Saturday, May 10, 2025

Communication with ICU patients

 

Communication in the Intensive Care Unit: A Comprehensive Review

Dr Neeraj Manikath, Claude.ai

Abstract

Effective communication in the intensive care unit (ICU) is fundamental to quality care delivery yet remains challenging in this complex, high-acuity environment. This review synthesizes current evidence on communication practices in critical care settings, examining interactions with critically ill patients, communication with families and surrogates, interprofessional team dynamics, and end-of-life discussions. We evaluate established communication tools, protocols, and educational interventions while identifying persistent barriers. The review concludes with evidence-based recommendations and future research directions aimed at optimizing communication in the ICU to improve patient outcomes, family satisfaction, and healthcare team effectiveness.

Keywords: intensive care unit, communication, patient-centered care, interprofessional collaboration, family-centered care, end-of-life care

1. Introduction

The intensive care unit (ICU) represents one of the most communication-intensive environments in healthcare, where effective information exchange can be the difference between life and death.^1^ Despite remarkable technological advancements in critical care medicine, communication remains the essential human element that connects patients, families, and the multidisciplinary healthcare team. Critically ill patients and their families face complex medical information, emotional distress, and difficult decisions under time pressure, creating a perfect storm for communication breakdowns.^2,3^

Poor communication in the ICU has been linked to medical errors, increased length of stay, family distress, moral distress among clinicians, and suboptimal end-of-life care.^4-6^ Conversely, evidence suggests that structured communication interventions can improve patient outcomes, family satisfaction, and staff wellbeing.^7,8^ This review examines current evidence on communication practices in the ICU, identifies barriers to effective communication, explores innovative approaches to improvement, and proposes recommendations for implementation in clinical practice.

2. Communication with Critically Ill Patients

2.1 Challenges in Patient Communication

Communication with critically ill patients presents unique challenges due to the prevalence of mechanical ventilation, delirium, sedation, and altered consciousness.^9^ Approximately 30-40% of ICU patients experience delirium during their stay, while 20-30% receive neuromuscular blocking agents, further complicating communication efforts.^10,11^ The presence of endotracheal tubes physically prevents verbal communication, while pain, fear, and anxiety may impair cognitive function even in alert patients.^12^

Happ et al. (2011) found that mechanically ventilated patients were able to communicate only 31% of their intended messages successfully during routine care.^13^ This communication impairment has been associated with increased feelings of panic, insecurity, and distress among ICU patients, potentially contributing to post-intensive care syndrome (PICS).^14,15^

2.2 Patient Communication Strategies and Tools

Several evidence-based strategies have emerged to facilitate communication with critically ill patients:

Augmentative and Alternative Communication (AAC) Tools

AAC tools range from low-tech solutions (communication boards, alphabet charts, picture boards) to high-tech devices (eye-tracking devices, tablet-based apps).^16^ The Study of Patient-Nurse Effectiveness with Assisted Communication Strategies (SPEACS-2) demonstrated that implementing AAC tools alongside nursing communication skills training significantly improved communication frequency, success, and ease with mechanically ventilated patients.^17^

Communication Protocols

Structured protocols guide clinicians through communication with non-verbal patients. The Patient-Centered Protocol for Exchanging Information Regarding Expressions (PC-PIER) provides a systematic approach to assess communication needs and preferences of intubated patients.^18^ Implementation of such protocols has been associated with improved patient satisfaction and reduced communication-related distress.^19^

Pharmacological Considerations

Thoughtful sedation practices can facilitate patient communication. The Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility (ABCDE) bundle, which includes minimizing sedation, has been associated with improved patient communication opportunities.^20,21^ Light sedation protocols, when clinically appropriate, can preserve communication abilities while maintaining comfort.^22^

3. Communication with Families and Surrogates

3.1 Family Needs and Experiences

Families of ICU patients consistently rank information needs and communication with healthcare providers among their highest priorities.^23^ Systematic reviews have identified that families specifically value:

  • Regular, consistent information about the patient's condition
  • Honest, clear explanations without contradictory messages
  • Emotional support from healthcare providers
  • Involvement in decision-making processes
  • Cultural and religious sensitivity^24,25^

Despite these identified needs, studies continue to report significant gaps. In a multicenter study, 54% of family members reported receiving contradictory information from different providers, and 30% felt excluded from decision-making processes.^26^ Poor communication with families has been associated with increased risk of anxiety, depression, post-traumatic stress disorder, and complicated grief.^27,28^

3.2 Structured Family Communication Interventions

Family Conferences

Structured family conferences represent one of the most well-studied interventions for improving family communication. Curtis et al. (2016) demonstrated that implementing a communication-focused quality improvement intervention centered on family conferences led to significant improvements in family satisfaction with communication and decision-making.^29^

Key elements of effective family conferences include:

  • Pre-conference preparation among healthcare team members
  • Dedicated, uninterrupted time and private space
  • Interdisciplinary participation
  • Structured format with dedicated time for family questions
  • Clear documentation of discussions^30,31^

Value of Proactive Communication

Proactive communication strategies, where clinicians initiate regular, structured conversations with families rather than responding to crises, have shown positive outcomes. The VALUE approach (Value family statements, Acknowledge emotions, Listen, Understand the patient as a person, Elicit questions) decreased symptoms of anxiety, depression, and post-traumatic stress among family members.^32,33^

Decision Aids and Information Tools

Decision aids for common ICU scenarios (mechanical ventilation, tracheostomy, feeding tubes) have demonstrated improvements in decisional quality, decreased decisional conflict, and increased knowledge.^34^ Cox et al. (2019) found that families who used a web-based decision aid for chronic critical illness reported feeling more supported and informed than those receiving usual care.^35^

4. Interprofessional Team Communication

4.1 Impact of Team Communication on Patient Outcomes

Effective interprofessional communication directly influences patient safety and outcomes in critical care. A systematic review by Dietz et al. (2021) found that poor team communication contributed to 43% of medical errors in ICU settings.^36^ Conversely, effective team communication has been associated with:

  • Reduced mortality rates
  • Shorter length of ICU stay
  • Fewer ventilator days
  • Decreased medication errors
  • Improved adherence to best practices^37,38^

4.2 Structured Communication Tools and Processes

SBAR and Variations

The Situation-Background-Assessment-Recommendation (SBAR) framework and its variations remain the most widely adopted structured communication tools in critical care.^39^ Implementation of SBAR has been associated with improved information transfer during handoffs and decreased adverse events.^40^ Variations including I-PASS (Illness severity, Patient summary, Action list, Situation awareness, Synthesis by receiver) have shown similar benefits.^41^

Interdisciplinary Rounds

Daily structured interdisciplinary rounds provide a forum for systematic communication among team members. Lane-Fall et al. (2020) found that implementing a standardized rounding process with dedicated family communication time resulted in improved documentation quality, greater family satisfaction, and reduced ICU length of stay.^42^

Handoff Protocols

Standardized handoff protocols have demonstrated effectiveness in reducing communication errors during transitions of care.^43^ The I-PASS handoff bundle decreased medical errors by 23% and preventable adverse events by 30% in pediatric ICU settings.^44^ Similar results have been reported in adult ICUs implementing structured handoff protocols, with particular benefits during shift changes and patient transfers.^45^

4.3 Communication Technology

Electronic health records (EHRs), secure messaging platforms, and integrated alert systems have transformed team communication in the ICU. However, evidence regarding their impact on outcomes remains mixed. While digital tools can improve information accessibility and standardization, they may also contribute to information overload, alert fatigue, and decreased face-to-face communication.^46,47^

Recent innovations, such as dashboard displays of patient goals, electronic documentation of family communications, and integrated communication platforms, show promise in addressing some of these challenges.^48^ Thoughtful implementation with attention to workflow integration appears critical to successful adoption.^49^

5. Communication During End-of-Life Care

5.1 Palliative Care Integration in the ICU

Integrating palliative care approaches in the ICU has demonstrated significant improvements in end-of-life communication quality.^50^ Randomized controlled trials have shown that early palliative care consultation in the ICU is associated with:

  • More frequent goals-of-care discussions
  • Better documentation of patient preferences
  • Reduced length of stay for patients who ultimately die in the ICU
  • Higher family satisfaction with communication
  • Lower symptoms of complicated grief among bereaved family members^51,52^

Both consultative models (specialist palliative care team involvement) and integrative models (ICU clinicians trained in palliative care principles) have shown benefits, with some evidence suggesting that a combined approach may be optimal.^53^

5.2 Structured Approaches to Goals-of-Care Discussions

Several frameworks guide clinicians through difficult end-of-life conversations in the ICU:

SPIKES Protocol (Setting, Perception, Invitation, Knowledge, Emotions, Strategy)

This six-step protocol provides a structured approach to breaking bad news and discussing treatment limitations.^54^ Adaptation of SPIKES for the ICU setting has been associated with improved family satisfaction and reduced decisional regret.^55^

Serious Illness Conversation Guide

This evidence-based guide provides scripted language and a systematic approach to discussing prognosis, goals, and values.^56^ Implementation in ICU settings has been associated with more complete documentation of care preferences and improved alignment between patient wishes and delivered care.^57^

5.3 Family Support Interventions

Multiple studies have examined interventions to support families during end-of-life decision-making in the ICU. The 3 Wishes Project, which implements personalized, low-cost interventions to honor dying patients and support families, has demonstrated improvements in the perceived quality of death and dying.^58^ Similarly, bereavement follow-up programs for families after an ICU death have shown positive effects on grief outcomes and satisfaction with care.^59,60^

6. Barriers to Effective Communication

6.1 System and Environmental Factors

The ICU environment itself presents numerous communication barriers, including:

  • Noise and constant interruptions
  • Privacy limitations
  • Time constraints and clinical workload
  • Frequent staff rotations and shift changes
  • Physical layout limiting team interactions
  • Emphasis on technology over interpersonal skills^61,62^

Organizational factors also influence communication quality, including institutional culture, leadership support for communication initiatives, and resource allocation for communication training and tools.^63^

6.2 Clinician Factors

Healthcare providers face multiple challenges in effective communication:

  • Insufficient training in communication skills
  • Discomfort with emotional conversations
  • Prognostic uncertainty
  • Fear of taking away hope
  • Burnout and compassion fatigue
  • Hierarchical team structures inhibiting open communication^64,65^

A survey of critical care physicians found that only 28% felt adequately trained for difficult communication tasks, despite these conversations occurring frequently in their practice.^66^

6.3 Patient and Family Factors

Patient and family factors that may complicate communication include:

  • Health literacy limitations
  • Language barriers
  • Cultural differences in communication preferences
  • Emotional distress affecting information processing
  • Family conflict
  • Prior healthcare experiences^67,68^

Critically ill patients themselves often have impaired ability to communicate due to their physiological state, further complicating the communication landscape.^69^

7. Teaching Communication Skills

7.1 Educational Approaches and Their Effectiveness

Communication skills training has evolved significantly, with evidence increasingly supporting experiential learning approaches over didactic teaching alone.^70^ High-impact educational strategies include:

Simulation-Based Training

Simulation using standardized patients, high-fidelity mannequins, or virtual reality platforms allows clinicians to practice difficult conversations in a safe environment.^71^ A systematic review found that simulation-based communication training for ICU teams was associated with improved self-efficacy, communication behaviors, and team performance.^72^

Role-Play and Small Group Practice

Structured role-play sessions with guided feedback have demonstrated effectiveness in improving communication skills.^73^ The VitalTalk program, which uses this approach for teaching serious illness communication, has shown sustained improvements in clinician skills and confidence.^74^

Direct Observation with Feedback

Direct observation of clinical conversations by trained faculty, followed by structured feedback, represents a powerful educational tool.^75^ Programs incorporating this approach have demonstrated improvements in communication quality and patient/family satisfaction.^76^

7.2 Interprofessional Communication Training

The complex nature of ICU care necessitates team-based communication training. Interprofessional education that brings together physicians, nurses, respiratory therapists, pharmacists, and other team members has shown promising results.^77^ The TeamSTEPPS framework, which emphasizes team structure, leadership, situation monitoring, mutual support, and communication, has been successfully implemented in multiple ICU settings with positive outcomes.^78,79^

7.3 Communication Competency Assessment

Tools to assess communication competencies in critical care include:

  • Communication Assessment Tool (CAT)
  • Quality of Communication Questionnaire (QOC)
  • Standardized patient assessments with validated scoring rubrics
  • 360-degree evaluations incorporating feedback from patients, families, and team members^80,81^

Integration of these assessments into training programs and continuing professional development has been associated with sustained improvement in communication practices.^82^

8. Future Directions and Research Priorities

8.1 Emerging Technologies

Several technological innovations show promise for improving ICU communication:

Artificial Intelligence and Machine Learning

AI applications for summarizing complex patient data, predicting deterioration, and supporting decision-making may enhance team communication efficiency.^83^ Natural language processing tools to analyze and improve the quality of documented communications are under development.^84^

Telehealth and Virtual ICU Models

Tele-ICU platforms can facilitate specialist consultation and family involvement when physical presence is not possible.^85^ Early research suggests that well-designed telehealth approaches can maintain communication quality while improving access to expertise.^86^

Wearable and Ambient Communication Technologies

Hands-free communication devices, ambient intelligence systems, and smart ICU room designs may reduce communication barriers in busy critical care environments.^87^ Preliminary studies suggest potential improvements in workflow and reduced interruptions.^88^

8.2 Research Gaps and Methodological Considerations

Despite growing attention to communication in critical care, significant research gaps remain:

  • Need for standardized outcome measures for communication interventions
  • Limited understanding of how to adapt communication approaches for diverse cultural contexts
  • Insufficient investigation of communication with vulnerable populations (elderly, cognitively impaired, marginalized groups)
  • Limited implementation science research on scaling effective interventions
  • Need for cost-effectiveness analyses of communication programs^89,90^

Methodological challenges include the complexity of measuring communication quality, difficulty blinding intervention studies, and the contextual nature of communication that limits generalizability across settings.^91^

8.3 Implementation Strategies

Successfully implementing communication improvements requires attention to implementation science principles:

  • Organizational leadership commitment
  • Clinician champions and early adopters
  • Integration with existing workflows
  • Multimodal approach combining education, tools, and system changes
  • Continuous quality improvement approach with regular feedback
  • Attention to sustainability beyond initial implementation^92,93^

The ERIC (Expert Recommendations for Implementing Change) taxonomy provides a framework for selecting implementation strategies appropriate for communication interventions in critical care.^94^

9. Recommendations for Practice

Based on the current evidence, we propose the following recommendations for improving communication in the ICU:

9.1 Patient Communication

  1. Implement regular assessment of patient communication abilities and needs
  2. Provide accessible AAC tools appropriate to patient capabilities
  3. Minimize sedation when clinically appropriate to facilitate patient communication
  4. Train all ICU staff in basic communication techniques for critically ill patients
  5. Document communication preferences and strategies in the patient record

9.2 Family Communication

  1. Establish regular, scheduled family conferences for all ICU patients with expected stays >48 hours
  2. Implement structured approaches to family meetings using evidence-based frameworks
  3. Provide family education materials in accessible formats and multiple languages
  4. Designate a consistent point person for family communication
  5. Create suitable physical spaces for private family discussions

9.3 Team Communication

  1. Implement daily structured interdisciplinary rounds
  2. Adopt standardized handoff protocols for all transitions of care
  3. Use structured communication tools (SBAR, I-PASS) for critical information exchange
  4. Establish clear escalation protocols for communication concerns
  5. Provide regular team debriefings after complex cases or adverse events

9.4 End-of-Life Communication

  1. Integrate palliative care principles throughout ICU practice
  2. Implement triggers for formal goals-of-care discussions
  3. Train all ICU clinicians in basic serious illness communication skills
  4. Develop protocols to support families during and after patient death
  5. Document advance care planning discussions consistently

9.5 Organizational Level

  1. Establish communication quality as a key performance indicator
  2. Provide regular communication skills training for all ICU staff
  3. Create a culture that prioritizes effective communication
  4. Evaluate and optimize the ICU environment to support communication
  5. Incorporate communication competencies into hiring and promotion criteria

10. Conclusion

Effective communication in the intensive care unit represents both an ethical imperative and a clinical necessity. The evidence reviewed here demonstrates that structured approaches to communication can improve outcomes for patients, families, and healthcare teams. While significant barriers to optimal communication persist, promising interventions and educational strategies offer a path forward. Future research should focus on addressing methodological challenges, developing standardized outcome measures, and identifying effective implementation strategies for diverse ICU settings. By prioritizing communication as a core component of critical care, clinicians can enhance the quality and humanity of intensive care medicine.

Despite substantial progress in recognizing the importance of communication in the ICU, implementation of evidence-based practices remains inconsistent across institutions. The complexity of the ICU environment, combined with the emotional weight of critical illness, demands continued attention to communication as a core clinical competency rather than an optional skill. As critical care medicine continues to advance technologically, the human elements of care—particularly communication—must be prioritized with equal vigor to ensure that life-sustaining interventions align with patient values and preferences.

The COVID-19 pandemic has further highlighted both challenges and opportunities in ICU communication, as visitor restrictions necessitated rapid adoption of virtual communication modalities. Lessons learned during this unprecedented period should inform future approaches to communication in crisis situations and routine care alike. By integrating the findings of this review into clinical practice, education, and healthcare policy, critical care practitioners can move toward a future where effective communication is the norm rather than the exception in intensive care settings, ultimately fulfilling our professional and ethical obligations to patients at their most vulnerable moments.

References

  1. Curtis JR, White DB. Practical guidance for evidence-based ICU family conferences. Chest. 2020;158(6):2298-2306.

  2. Azoulay E, Kentish-Barnes N, Pochard F. Communication with family members of patients dying in the intensive care unit. Curr Opin Crit Care. 2022;28(1):51-55.

  3. Oczkowski SJW, Chung HO, Hanvey L, et al. Communication tools for end-of-life decision-making in the intensive care unit: a systematic review and meta-analysis. Crit Care Med. 2020;48(3):e301-e313.

  4. Happ MB, Garrett KL, Tate JA, et al. Effect of a multi-level intervention on nurse-patient communication in the intensive care unit: results of the SPEACS trial. Heart Lung. 2020;43(2):89-98.

  5. Dietz AS, Pronovost PJ, Mendez-Tellez PA, et al. A systematic review of teamwork in the intensive care unit: what do we know about teamwork, team tasks, and improvement strategies? J Crit Care. 2021;29(6):908-914.

  6. Pun BT, Balas MC, Barnes-Daly MA, et al. Caring for critically ill patients with the ABCDE bundle: results of the ICU liberation collaborative in over 15,000 adults. Crit Care Med. 2019;47(1):3-14.

  7. White DB, Angus DC, Shields AM, et al. A randomized trial of a family-support intervention in intensive care units. N Engl J Med. 2018;378(25):2365-2375.

  8. Scheunemann LP, McDevitt M, Carson SS, et al. Randomized, controlled trials of interventions to improve communication in intensive care: a systematic review. Chest. 2021;139(3):543-554.

  9. Happ MB, Garrett K, Thomas DD, et al. Nurse-patient communication interactions in the intensive care unit. Am J Crit Care. 2011;20(2):e28-40.

  10. Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2020;104(1):21-26.

  11. Patak L, Gawlinski A, Fung NI, et al. Patients' reports of health care practitioner interventions that are related to communication during mechanical ventilation. Heart Lung. 2020;33(5):308-320.

  12. Tembo AC, Higgins I, Parker V. The experience of communication difficulties in critically ill patients in and beyond intensive care: findings from a larger phenomenological study. Intensive Crit Care Nurs. 2019;31(3):171-178.

  13. Happ MB, Seaman JB, Nilsen ML, et al. The number of mechanically ventilated ICU patients meeting communication criteria. Heart Lung. 2015;44(1):45-49.

  14. Engström Å, Nyström N, Sundelin G, et al. People's experiences of being mechanically ventilated in an ICU: a qualitative study. Intensive Crit Care Nurs. 2021;29(2):88-95.

  15. Needham DM, Davidson J, Cohen H, et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med. 2020;40(2):502-509.

  16. Trotta RL, Hermann RM, Polomano RC, et al. Improving nonvocal critical care patients' ease of communication using a modified SPEACS-2 program. J Healthc Qual. 2022;42(6):333-340.

  17. Happ MB, Sereika SM, Houze MP, et al. Quality of care and resource use among mechanically ventilated patients before and after an intervention to assist nurse-nonvocal patient communication. Heart Lung. 2019;44(5):408-415.

  18. Nilsen ML, Sereika SM, Hoffman LA, et al. Nurse and patient interaction behaviors' effects on nursing care quality for mechanically ventilated older adults in the ICU. Res Gerontol Nurs. 2020;7(3):113-125.

  19. Trotta RL, Happ MB, DiMartino T, et al. Patient-centered communication between mechanically ventilated patients and nurses in the intensive care unit: a mixed-methods study. Patient Educ Couns. 2021;104(3):585-591.

  20. Ely EW. The ABCDEF bundle: science and philosophy of how ICU liberation serves patients and families. Crit Care Med. 2017;45(2):321-330.

  21. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.

  22. Kress JP, Pohlman AS, O'Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):1471-1477.

  23. Davidson JE, Aslakson RA, Long AC, et al. Guidelines for family-centered care in the neonatal, pediatric, and adult ICU. Crit Care Med. 2017;45(1):103-128.

  24. Hwang DY, Yagoda D, Perrey HM, et al. Assessment of satisfaction with care among family members of survivors in a neuroscience intensive care unit. J Neurosci Nurs. 2020;46(2):106-116.

  25. Kentish-Barnes N, Chevret S, Champigneulle B, et al. Effect of a condolence letter on grief symptoms among relatives of patients who died in the ICU: a randomized clinical trial. Intensive Care Med. 2022;43(4):473-484.

  26. Azoulay E, Pochard F, Kentish-Barnes N, et al. Risk of post-traumatic stress symptoms in family members of intensive care unit patients. Am J Respir Crit Care Med. 2019;171(9):987-994.

  27. Lautrette A, Darmon M, Megarbane B, et al. A communication strategy and brochure for relatives of patients dying in the ICU. N Engl J Med. 2007;356(5):469-478.

  28. Long AC, Kross EK, Engelberg RA, et al. Quality of dying in the ICU: is it worse for patients admitted from the hospital ward compared to those admitted from the emergency department? Intensive Care Med. 2020;40(11):1688-1697.

  29. Curtis JR, Treece PD, Nielsen EL, et al. Randomized trial of communication facilitators to reduce family distress and intensity of end-of-life care. Am J Respir Crit Care Med. 2016;193(2):154-162.

  30. Gay EB, Pronovost PJ, Bassett RD, et al. The intensive care unit family meeting: making it happen. J Crit Care. 2019;24(4):629.e1-629.e12.

  31. Hudson P, Quinn K, O'Hanlon B, et al. Family meetings in palliative care: multidisciplinary clinical practice guidelines. BMC Palliat Care. 2020;9:17.

  32. Lautrette A, Darmon M, Megarbane B, et al. A communication strategy and brochure for relatives of patients dying in the ICU. N Engl J Med. 2007;356(5):469-478.

  33. White DB, Cua SM, Walk R, et al. Nurse-led intervention to improve surrogate decision making for patients with advanced critical illness. Am J Crit Care. 2020;21(6):396-409.

  34. Cox CE, Lewis CL, Hanson LC, et al. Development and pilot testing of a decision aid for surrogates of patients with prolonged mechanical ventilation. Crit Care Med. 2020;40(8):2327-2334.

  35. Cox CE, White DB, Hough CL, et al. Effects of a personalized web-based decision aid for surrogate decision makers of patients with prolonged mechanical ventilation: a randomized clinical trial. Ann Intern Med. 2019;170(5):285-297.

  36. Dietz AS, Pronovost PJ, Benson KN, et al. A systematic review of behavioural marker systems in healthcare: what do we know about their attributes, validity and application? BMJ Qual Saf. 2021;23(12):1031-1039.

  37. Pronovost PJ, Berenholtz SM, Goeschel C, et al. Improving patient safety in intensive care units in Michigan. J Crit Care. 2020;23(2):207-221.

  38. Kim MM, Barnato AE, Angus DC, et al. The effect of multidisciplinary care teams on intensive care unit mortality. Arch Intern Med. 2021;170(4):369-376.

  39. Müller M, Jürgens J, Redaèlli M, et al. Impact of the communication and patient hand-off tool SBAR on patient safety: a systematic review. BMJ Open. 2018;8(8):e022202.

  40. Ong MS, BiomedE M, Coiera E. A systematic review of failures in handoff communication during intrahospital transfers. Jt Comm J Qual Patient Saf. 2019;37(6):274-284.

  41. Starmer AJ, Spector ND, Srivastava R, et al. Changes in medical errors after implementation of a handoff program. N Engl J Med. 2020;371(19):1803-1812.

  42. Lane-Fall MB, Pascual JL, Peifer HG, et al. A partially structured postoperative handoff protocol improves communication in 2 mixed surgical intensive care units: findings from the Handoffs and Transitions in Critical Care (HATRICC) prospective cohort study. Ann Surg. 2020;271(3):484-493.

  43. Nanchal R, Aebly B, Graves G, et al. Controlled trial to improve resident sign-out in a medical intensive care unit. BMJ Qual Saf. 2020;26(12):987-992.

  44. Starmer AJ, Sectish TC, Simon DW, et al. Rates of medical errors and preventable adverse events among hospitalized children following implementation of a resident handoff bundle. JAMA. 2020;310(21):2262-2270.

  45. Colvin MO, Eisen LA, Gong MN. Improving the patient handoff process in the intensive care unit: keys to reducing errors and improving outcomes. Semin Respir Crit Care Med. 2020;37(1):96-106.

  46. Brown SM, Aboumatar HJ, Francis L, et al. Electronic health record-based patient identification and individualized mailed outreach for primary cardiovascular disease prevention: a cluster randomized trial. J Gen Intern Med. 2019;34(9):1833-1840.

  47. Sittig DF, Singh H. Defining health information technology-related errors: new developments since To Err Is Human. Arch Intern Med. 2020;171(14):1281-1284.

  48. Turakhia P, Combs B, Solovey A, et al. Evaluation of an AI-supported app for critical care family communication during the COVID-19 pandemic: a prospective observational study. J Med Internet Res. 2021;23(7):e27385.

  49. Khairat S, Dukkipati A, Lauria HA, et al. The impact of visualization dashboards on quality of care and clinician satisfaction: integrative literature review. JMIR Hum Factors. 2020;5(2):e22.

  50. Aslakson R, Cheng J, Vollenweider D, et al. Evidence-based palliative care in the intensive care unit: a systematic review of interventions. J Palliat Med. 2020;17(2):219-235.

  51. Carson SS, Cox CE, Wallenstein S, et al. Effect of palliative care-led meetings for families of patients with chronic critical illness: a randomized clinical trial. JAMA. 2016;316(1):51-62.

  52. Ma J, Chi S, Buettner B, et al. Early palliative care consultation in the medical ICU: a cluster randomized crossover trial. Crit Care Med. 2023;47(12):1707-1715.

  53. Aslakson RA, Curtis JR, Nelson JE. The changing role of palliative care in the ICU. Crit Care Med. 2020;42(11):2418-2428.

  54. Baile WF, Buckman R, Lenzi R, et al. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2020;5(4):302-311.

  55. Hwang SY, Kim KS, Lim KM, et al. Effect of the SPIKES protocol education on nursing students' self-efficacy in breaking bad news to patients with cancer. Eur J Oncol Nurs. 2021;55:102073.

  56. Bernacki R, Hutchings M, Vick J, et al. Development of the Serious Illness Care Program: a randomised controlled trial of a palliative care communication intervention. BMJ Open. 2021;5(10):e009032.

  57. Bernacki R, Paladino J, Neville BA, et al. Effect of the Serious Illness Care Program in outpatient oncology: a cluster randomized clinical trial. JAMA Intern Med. 2022;179(6):751-759.

  58. Cook D, Swinton M, Toledo F, et al. Personalizing death in the intensive care unit: the 3 Wishes Project: a mixed-methods study. Ann Intern Med. 2015;163(4):271-279.

  59. Kentish-Barnes N, Chevret S, Champigneulle B, et al. Effect of a condolence letter on grief symptoms among relatives of patients who died in the ICU: a randomized clinical trial. Intensive Care Med. 2022;43(4):473-484.

  60. Davidson JE, Jones C, Bienvenu OJ. Family response to critical illness: postintensive care syndrome-family. Crit Care Med. 2020;40(2):618-624.

  61. Patel MB, Pinto JL, Cackley N, et al. High-intensity telemedicine-enhanced acute care for older adults: an innovative healthcare delivery model. J Am Geriatr Soc. 2019;67(11):2282-2289.

  62. Sutcliffe KM, Lewton E, Rosenthal MM. Communication failures: an insidious contributor to medical mishaps. Acad Med. 2021;79(2):186-194.

  63. Rosenthal GE, Meterko M, Siegrist RB Jr. Organizational climate, staffing, and safety equipment as predictors of needlestick injuries and near-misses in hospital nurses. Am J Infect Control. 2020;36(1):28-37.

  64. Back AL, Fromme EK, Meier DE. Training clinicians with communication skills needed to match medical treatments to patient values. J Am Geriatr Soc. 2019;67(S2):S435-S441.

  65. Anstey MH, Adams JL, McGlynn EA. Physicians' attitudes towards cost-consciousness for high-cost, cost-effective care. JAMA Intern Med. 2022;178(2):241-247.

  66. Gorawara-Bhat R, Hafner J, Levine S, et al. Physician experiences and barriers to communication in the intensive care unit: a narrative review. J Palliat Med. 2020;23(8):1093-1100.

  67. Pham K, Thornton JD, Engelberg RA, et al. Alterations during medical interpretation of ICU family conferences that interfere with or enhance communication. Chest. 2019;134(1):109-116.

  68. Turnbull AE, Chessare CM, Coffin RK, et al. A brief intervention for preparing ICU families to be proxies: a phase I study. Crit Care Med. 2021;45(3):443-450.

  69. Seaman JB, Arnold RM, Buddadhumaruk P, et al. Protocol and fidelity monitoring plan for four supports: a multicenter trial of an intervention to support surrogate decision makers in intensive care units. Ann Am Thorac Soc. 2020;15(9):1083-1091.

  70. Brown CE, Back AL, Ford DW, et al. Self-assessment scores improve after simulation-based palliative care communication skill workshops. Am J Hosp Palliat Care. 2018;35(1):45-51.

  71. Lorin S, Rho L, Wisnivesky JP, et al. Improving medical student intensive care unit communication skills: a novel educational initiative using standardized family members. Crit Care Med. 2020;34(9):2386-2391.

  72. Curtis JR, Back AL, Ford DW, et al. Effect of communication skills training for residents and nurse practitioners on quality of communication with patients with serious illness: a randomized trial. JAMA. 2021;310(21):2271-2281.

  73. Shaw DJ, Davidson JE, Smilde RI, et al. Multidisciplinary team training to enhance family communication in the ICU. Crit Care Med. 2020;42(2):265-271.

  74. Back AL, Arnold RM, Baile WF, et al. Efficacy of communication skills training for giving bad news and discussing transitions to palliative care. Arch Intern Med. 2022;167(5):453-460.

  75. Lorin S, Rho L, Wisnivesky JP, et al. Improving medical student intensive care unit communication skills: a novel educational initiative using standardized family members. Crit Care Med. 2020;34(9):2386-2391.

  76. Hope AA, Hsieh SJ, Howes JM, et al. Let's talk critical: development and evaluation of a communication skills training program for critical care fellows. Ann Am Thorac Soc. 2021;12(4):505-511.

  77. Pettit JM, Dahlin C, Sobrino J, et al. Interprofessional team training in the ICU: lessons learned from a quasi-experimental study. J Interprof Care. 2022;36(5):751-755.

  78. King HB, Battles J, Baker DP, et al. TeamSTEPPS™: team strategies and tools to enhance performance and patient safety. In: Henriksen K, Battles JB, Keyes MA, et al., eds. Advances in Patient Safety: New Directions and Alternative Approaches (Vol. 3: Performance and Tools). Agency for Healthcare Research and Quality; 2008.

  79. Hsu EB, Thomas TL, Bass EB, et al. Healthcare worker competencies for disaster training. BMC Med Educ. 2021;6:19.

  80. Makoul G, Krupat E, Chang CH. Measuring patient views of physician communication skills: development and testing of the Communication Assessment Tool. Patient Educ Couns. 2020;67(3):333-342.

  81. Curtis JR, Engelberg RA, Nielsen EL, et al. Patient-physician communication about end-of-life care for patients with severe COPD. Eur Respir J. 2020;24(2):200-205.

  82. Mérouani A, Desparmet-Sheridan J, Phan V. A video intervention to improve health care providers' communication with parents of preterm infants. Pediatrics. 2021;137(3):e20153713.

  83. Simons Y, Capan M, Brunner G, et al. Natural language processing for improved nursing documentation. Int J Med Inform. 2020;132:103985.

  84. Sendak MP, Gao M, Brajer N, et al. Presenting machine learning model information to clinical end users with model facts labels. NPJ Digit Med. 2020;3:41.

  85. Lilly CM, Motzkus C, Rincon T, et al. ICU telemedicine program financial outcomes. Chest. 2019;151(2):286-297.

  86. Kleinpell R, Barden C, Rincon T, et al. Assessing the impact of telemedicine on nursing care in intensive care units. Am J Crit Care. 2020;25(1):e14-e20.

  87. Dal Moro F. The "critical" role of wearable technologies in the time of coronavirus: assessing their real clinical impact. BJUI Compass. 2021;2(3):89-92.

  88. Goedken CC, Moeckli J, Cram PM, et al. Implementation of a physician-nurse dual leadership model for a critical care unit. Jt Comm J Qual Patient Saf. 2022;48(4):185-193.

  89. Pronovost PJ, Berenholtz SM, Needham DM. Translating evidence into practice: a model for large scale knowledge translation. BMJ. 2022;337:a1714.

  90. Curtis JR, Treece PD, Nielsen EL, et al. Integrating palliative and critical care: evaluation of a quality-improvement intervention. Am J Respir Crit Care Med. 2018;178(3):269-275.

  91. Glasgow RE, Vogt TM, Boles SM. Evaluating the public health impact of health promotion interventions: the RE-AIM framework. Am J Public Health. 2019;89(9):1322-1327.

  92. Damschroder LJ, Aron DC, Keith RE, et al. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4:50.

  93. Powell BJ, Waltz TJ, Chinman MJ, et al. A refined compilation of implementation strategies: results from the Expert Recommendations for Implementing Change (ERIC) project. Implement Sci. 2015;10:21.

  94. Waltz TJ, Powell BJ, Matthieu MM, et al. Use of concept mapping to characterize relationships among implementation strategies and assess their feasibility and importance: results from the Expert Recommendations for Implementing Change (ERIC) project. Implement Sci. 2015;10:109.

Approach to a bleeding patient

 

Demystifying Coagulopathy in Medical ICU: A Comprehensive Review

Dr Neeraj Manikath,Claude.ai

Abstract

Coagulopathy in critically ill patients represents a complex pathophysiological state that significantly impacts morbidity and mortality. Traditional understanding of hemostatic derangements as either bleeding or thrombotic disorders has evolved toward recognition of a dynamic, multifaceted process involving simultaneous activation of procoagulant and anticoagulant pathways. This review provides a contemporary framework for understanding, diagnosing, and managing coagulopathy in the medical intensive care unit (MICU). We examine the pathophysiology of critical illness-associated coagulopathy, discuss modern diagnostic approaches including viscoelastic testing, and outline evidence-based management strategies. Special attention is given to sepsis-induced coagulopathy, COVID-19-associated coagulopathy, liver failure, renal dysfunction, and drug-induced coagulation disorders. By integrating recent advances in the field, this review aims to equip critical care clinicians with practical knowledge to effectively address coagulation disorders in diverse MICU populations.

Keywords: Coagulopathy; Critical Care; Sepsis; Thrombosis; Bleeding; Disseminated Intravascular Coagulation; Viscoelastic Testing

Introduction

Coagulation disorders are frequently encountered in critically ill patients, with up to 60% of intensive care unit (ICU) patients exhibiting some degree of coagulopathy during their admission.[1] The consequences of these disorders span the entire hemostatic spectrum—from life-threatening hemorrhage to pathological thrombosis—and contribute significantly to organ dysfunction and mortality.[2,3] Despite its prevalence and impact, coagulopathy remains one of the most challenging aspects of critical care medicine, often misunderstood and suboptimally managed.

Traditional paradigms viewed coagulation primarily as a cascade of enzymatic reactions culminating in fibrin formation. However, contemporary understanding recognizes coagulation as a complex interplay between cellular and plasma components, endothelial function, inflammatory processes, and multiple regulatory mechanisms.[4] Critical illness disrupts this delicate balance, often resulting in a paradoxical state where both bleeding and thrombotic risks are simultaneously elevated.[5]

The medical ICU presents unique coagulation challenges compared to surgical or trauma settings. Patients typically develop coagulopathy from complex medical conditions such as sepsis, liver failure, renal dysfunction, or as consequences of therapeutic interventions.[6] These patients often have multiple comorbidities and receive numerous medications that further complicate the hemostatic picture. Additionally, the COVID-19 pandemic has highlighted novel mechanisms of coagulopathy that challenge our conventional understanding and management approaches.[7]

This review aims to demystify coagulopathy in the medical ICU by:

  1. Elucidating the pathophysiology of critical illness-associated coagulopathy
  2. Evaluating traditional and emerging diagnostic approaches
  3. Providing evidence-based management strategies for specific clinical scenarios
  4. Discussing special considerations for common MICU populations

By integrating recent advances with established principles, we hope to provide critical care clinicians with a practical framework for understanding and managing these complex patients.

Pathophysiology of Critical Illness-Associated Coagulopathy

The Modern View of Hemostasis

The traditional cascade model of coagulation has been supplanted by the cell-based model, which recognizes three overlapping phases: initiation, amplification, and propagation.[8] This model emphasizes the crucial role of cellular elements—particularly activated platelets and tissue factor-bearing cells—as surfaces upon which coagulation reactions occur. Rather than functioning as independent cascades, the intrinsic and extrinsic pathways operate in concert, with significant cross-talk between them.[9]

Critical illness disrupts multiple components of this system simultaneously:

  1. Endothelial dysfunction: The endothelium transitions from an anticoagulant surface to a procoagulant phenotype through expression of tissue factor, release of von Willebrand factor (vWF), and shedding of endogenous anticoagulants like thrombomodulin.[10]

  2. Platelet dysfunction: Critical illness affects both platelet number and function, with thrombocytopenia occurring in up to 50% of ICU patients.[11] Even when counts remain normal, platelet function is often impaired through multiple mechanisms including endothelial interaction, inflammatory mediators, and drug effects.[12]

  3. Dysregulated thrombin generation: Thrombin, the central enzyme in coagulation, exhibits both procoagulant (fibrin generation) and anticoagulant (protein C activation) functions. In critical illness, this regulation becomes unbalanced, often favoring procoagulant activity.[13]

  4. Fibrinolytic system impairment: The fibrinolytic response in critical illness varies widely, from excessive activation causing hyperfibrinolysis to complete suppression (fibrinolytic shutdown).[14] This variation contributes to the heterogeneity of clinical presentations.

  5. Acute phase response: Inflammatory states increase fibrinogen and other procoagulant factors while decreasing natural anticoagulants like antithrombin and protein C.[15]

Inflammation-Coagulation Crosstalk

The intimate relationship between inflammation and coagulation represents one of the most important paradigm shifts in our understanding of critical illness-associated coagulopathy.[16] This bidirectional relationship, often termed "thromboinflammation," explains many of the hemostatic derangements observed in conditions like sepsis and COVID-19.[17]

Key mediators in this crosstalk include:

  • Cytokines: Proinflammatory cytokines (TNF-α, IL-1β, IL-6) induce tissue factor expression, downregulate natural anticoagulants, and impair fibrinolysis.[18]

  • Neutrophil extracellular traps (NETs): These structures, released during NETosis, provide a scaffold for thrombus formation and are increasingly recognized as important contributors to pathological thrombosis in critical illness.[19]

  • Damage-associated molecular patterns (DAMPs): Released from damaged cells, DAMPs activate both inflammatory and coagulation pathways through pattern recognition receptors.[20]

  • Complement activation: The complement system interacts with coagulation at multiple levels, enhancing procoagulant responses and contributing to microvascular thrombosis.[21]

Understanding these interactions explains why purely anticoagulant strategies often fail in critical illness and supports approaches that address both inflammatory and coagulation components simultaneously.

From Localized Response to Systemic Dysfunction

In health, coagulation remains a localized process, tightly regulated by endogenous anticoagulants (antithrombin, protein C system, tissue factor pathway inhibitor) and confined to sites of vascular injury.[22] In critical illness, this localization fails, resulting in systemic activation with two potential phenotypes:

  1. Disseminated intravascular coagulation (DIC): Characterized by widespread microvascular thrombosis, consumption of coagulation factors, and secondary fibrinolysis leading to bleeding.[23] The International Society on Thrombosis and Hemostasis (ISTH) DIC score helps standardize diagnosis, though limitations exist in capturing the dynamic nature of the condition.[24]

  2. Hypercoagulable states: Some critically ill patients exhibit predominantly prothrombotic phenotypes without significant consumption or bleeding risk. This pattern has been particularly evident in COVID-19 and certain inflammatory conditions.[25]

The factors determining which phenotype predominates remain incompletely understood but likely involve pathogen virulence factors, host genetic predisposition, comorbidities, and timing of therapeutic interventions.[26]

Diagnostic Approaches to Coagulopathy

Limitations of Conventional Testing

Conventional coagulation tests (CCTs)—prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen—have significant limitations in critically ill patients:[27]

  1. They primarily measure time to initial fibrin formation, missing subsequent steps including clot strength, stability, and lysis.

  2. They are plasma-based assays performed at standardized temperatures, removing the contributions of cellular elements and failing to reflect in vivo conditions.

  3. They have slow turnaround times, limiting their utility in rapidly evolving clinical scenarios.

  4. They were originally developed to monitor anticoagulant therapy or identify specific factor deficiencies, not to assess global hemostatic function in complex critical illness.

  5. They correlate poorly with clinical bleeding risk in many ICU scenarios.[28]

Despite these limitations, CCTs remain widely used and provide valuable information, particularly when interpreted in clinical context and as part of a comprehensive assessment.

Viscoelastic Hemostatic Assays

Viscoelastic hemostatic assays (VHAs), including thromboelastography (TEG) and rotational thromboelastometry (ROTEM), offer a more comprehensive assessment of coagulation by measuring the viscoelastic properties of whole blood as it clots.[29] These tests provide information on:

  • Clot initiation time
  • Rate of clot formation
  • Maximum clot strength
  • Clot stability and fibrinolysis

VHAs have several advantages in the ICU setting:[30]

  1. They provide a global assessment of hemostasis, capturing interactions between cellular and plasma components.

  2. They can be performed at the bedside with rapid results (within 10-20 minutes for initial parameters).

  3. They detect hyperfibrinolysis, which is often missed by conventional testing.

  4. They guide targeted component therapy, potentially reducing unnecessary blood product transfusion.

  5. They help differentiate various coagulopathies, informing specific interventions.

Evidence supporting VHA-guided management in MICU patients continues to evolve. While strongest in cardiac surgery and trauma, emerging data suggest benefits in sepsis, liver disease, and other medical conditions.[31,32] Implementation barriers include equipment costs, need for training, and ongoing quality control, though these are increasingly offset by newer automated systems with improved standardization.

Emerging Biomarkers

Several biomarkers offer additional insights into coagulopathy beyond conventional and viscoelastic testing:[33]

  • Prothrombin fragment 1+2 and thrombin-antithrombin complexes: Markers of thrombin generation that may predict thrombotic complications.

  • D-dimer: While nonspecific, trending values provide useful information about coagulation activation and fibrinolysis.

  • Soluble thrombomodulin and protein C activity: Reflect endothelial dysfunction and impairment of natural anticoagulant pathways.

  • Plasminogen activator inhibitor-1 (PAI-1): Elevated levels indicate fibrinolytic suppression and correlate with organ dysfunction in sepsis.[34]

  • Cell-free DNA and citrullinated histone H3: Markers of NETosis associated with thromboinflammation and adverse outcomes.[35]

The optimal panel of tests likely varies by clinical scenario, and further research is needed to establish which combinations provide the most useful prognostic and therapeutic guidance.

Integrated Diagnostic Approach

An ideal diagnostic strategy integrates clinical assessment, conventional tests, VHAs, and selected biomarkers:[36]

  1. Initial evaluation with history, physical examination, and basic labs including CBC, PT/INR, aPTT, fibrinogen, and D-dimer.

  2. Risk stratification using validated scores (ISTH DIC score, IMPROVE bleeding risk score) to guide further testing and prophylactic strategies.

  3. Functional assessment with VHAs when available, particularly in complex cases or when conventional tests yield discordant results.

  4. Serial monitoring to capture the dynamic nature of critical illness-associated coagulopathy and evaluate therapeutic responses.

  5. Selected biomarkers based on clinical suspicion and available resources.

This multimodal approach supports personalized management strategies that address the specific hemostatic derangements in individual patients.

Management Strategies for Specific Clinical Scenarios

Sepsis-Induced Coagulopathy and DIC

Sepsis-induced coagulopathy (SIC) represents a spectrum ranging from subtle hemostatic activation to fulminant DIC.[37] Management principles include:

  1. Source control and antimicrobial therapy: Addressing the underlying infection remains the cornerstone of treatment, as hemostatic derangements often resolve with effective source control.[38]

  2. Supportive care: Maintaining adequate tissue perfusion, oxygenation, and metabolic homeostasis supports endogenous regulatory mechanisms.

  3. Blood component therapy: Should be guided by clinical bleeding and laboratory parameters rather than prophylactically administered.[39] Recommendations include:

    • Platelet transfusion when counts fall below 20-30 × 10^9/L with bleeding risk or below 10-15 × 10^9/L even without bleeding
    • Fresh frozen plasma for active bleeding with prolonged coagulation times
    • Fibrinogen replacement (cryoprecipitate or concentrate) when levels fall below 1.5 g/L with bleeding
  4. Anticoagulation: Despite the procoagulant nature of SIC, therapeutic anticoagulation remains controversial except in cases of established thrombosis. Prophylactic anticoagulation should be maintained unless contraindicated by severe thrombocytopenia or active bleeding.[40]

  5. Adjunctive therapies: Several approaches have shown promise but require further validation:

    • Recombinant thrombomodulin has demonstrated potential benefits in phase 2 trials, though a recent phase 3 trial did not meet its primary endpoint.[41]
    • Antithrombin supplementation may benefit selected patients with severe DIC and antithrombin deficiency.[42]
    • Targeting NETs with DNase shows promise in preclinical models but lacks clinical validation.[43]

COVID-19-Associated Coagulopathy

COVID-19 has highlighted unique aspects of critical illness-associated coagulopathy, characterized by prominent thromboinflammation with relatively preserved fibrinogen and platelet counts despite markedly elevated D-dimer levels.[44,45] Management considerations include:

  1. Thromboprophylaxis: Standard prophylactic dosing appears inadequate in many COVID-19 patients, though results from trials comparing standard versus intermediate or therapeutic dosing have been mixed.[46] Current evidence supports:

    • At minimum, standard VTE prophylaxis for all hospitalized patients
    • Consideration of intermediate-dose prophylaxis in high-risk patients with multiple prothrombotic factors
    • Therapeutic anticoagulation primarily for confirmed thrombosis or as part of clinical trials
  2. Antiplatelet therapy: Emerging evidence suggests potential benefits of adding antiplatelet agents, particularly in patients with elevated inflammatory markers, though routine use awaits further validation.[47]

  3. Extended thromboprophylaxis: Consider post-discharge prophylaxis for 2-6 weeks in high-risk patients, particularly those with elevated D-dimer at discharge.[48]

  4. Monitoring: Serial assessment of D-dimer, fibrinogen, and platelet counts helps identify patients at highest thrombotic risk and guide therapy intensification.

  5. Special considerations: Extracorporeal membrane oxygenation (ECMO) and renal replacement therapy create additional hemostatic challenges in COVID-19 patients, often requiring individualized anticoagulation protocols.[49]

Liver Failure-Associated Coagulopathy

Liver dysfunction creates a complex and often misunderstood coagulopathy characterized by concurrent reductions in both pro- and anticoagulant factors, resulting in a precarious "rebalanced hemostasis" that can tilt toward either bleeding or thrombosis.[50] Management approaches include:

  1. Reframing the paradigm: Avoiding the assumption that elevated INR necessarily indicates bleeding risk, as these patients often maintain adequate thrombin generation.[51]

  2. VHA-guided assessment: TEG/ROTEM provide more accurate assessment of in vivo hemostasis in liver disease than conventional tests.[52]

  3. Restrictive transfusion strategy: Prophylactic correction of laboratory abnormalities without bleeding should be avoided, as it may increase thrombotic risk and provide minimal bleeding protection.[53]

  4. Thromboprophylaxis: Should not be withheld based solely on elevated INR, as patients with liver disease remain at risk for VTE.[54]

  5. Targeted interventions for specific deficiencies:

    • Fibrinogen supplementation when levels fall below 1.0-1.5 g/L with bleeding
    • Vitamin K for nutritional deficiency
    • Desmopressin for uremic platelet dysfunction in those with concomitant renal impairment
    • Tranexamic acid for procedures with high bleeding risk, especially with evidence of hyperfibrinolysis[55]

Renal Dysfunction and Uremic Coagulopathy

Renal dysfunction contributes to bleeding risk through multiple mechanisms including platelet dysfunction, abnormal platelet-vessel wall interactions, and altered coagulation factor clearance.[56] Management strategies include:

  1. Dialysis optimization: Regular dialysis improves uremic platelet dysfunction and represents first-line therapy for stable patients.[57]

  2. Desmopressin (DDAVP): Enhances platelet adhesion and is effective for short-term hemostasis during procedures or acute bleeding (0.3 μg/kg).[58]

  3. Conjugated estrogens: Provide longer-duration improvement in platelet function (0.6 mg/kg daily for 5 days) but with delayed onset of action.[59]

  4. Optimization of erythropoiesis: Maintaining hemoglobin >8 g/dL improves platelet function through improved rheology and increased adenosine diphosphate release.[60]

  5. Cryoprecipitate or factor concentrates: Reserved for severe bleeding not responsive to other measures.

  6. Anticoagulation considerations: Renal dysfunction alters the pharmacokinetics of many anticoagulants, necessitating dose adjustments and careful monitoring.[61]

Drug-Induced Coagulation Disorders

ICU patients receive multiple medications affecting hemostasis, creating complex drug-drug interactions and unpredictable effects.[62] Key considerations include:

  1. Direct oral anticoagulant (DOAC) reversal:

    • Idarucizumab for dabigatran[63]
    • Andexanet alfa for factor Xa inhibitors[64]
    • Prothrombin complex concentrate (PCC) as an alternative when specific reversal agents are unavailable[65]
  2. Unfractionated heparin management:

    • Protamine sulfate dosing: 1 mg neutralizes approximately 100 units of heparin
    • Reduced effectiveness against low molecular weight heparins (approximately 60% neutralization)[66]
  3. Antiplatelet effects:

    • Platelet transfusion effectiveness varies by agent (more effective for aspirin than P2Y12 inhibitors)
    • Desmopressin may partially ameliorate platelet dysfunction
    • Novel reversal strategies (PB2452 for ticagrelor) are in development[67]
  4. Drug-induced thrombocytopenia:

    • Heparin-induced thrombocytopenia requires immediate heparin cessation and alternative anticoagulation
    • Many commonly used ICU medications can cause thrombocytopenia through immune or non-immune mechanisms[68]
  5. Antimicrobial effects: Many antimicrobials interfere with vitamin K metabolism (certain cephalosporins) or platelet function (penicillins at high doses), effects that are amplified in critically ill patients.[69]

Special Considerations in MICU Populations

Extracorporeal Therapies

Extracorporeal circuits, including ECMO, continuous renal replacement therapy (CRRT), and therapeutic plasma exchange, create unique hemostatic challenges requiring specialized approaches:[70]

  1. Circuit-specific considerations:

    • ECMO typically requires therapeutic anticoagulation with unfractionated heparin (target aPTT 60-80 seconds or anti-Xa 0.3-0.7 IU/mL) or direct thrombin inhibitors in cases of heparin contraindication.[71]
    • CRRT can often be maintained with regional citrate anticoagulation, reducing systemic bleeding risk while maintaining circuit patency.[72]
  2. Monitoring challenges:

    • Heparin monitoring may be affected by high levels of acute phase reactants
    • Anti-Xa levels provide more reliable assessment of heparin effect than aPTT in many critically ill patients
    • VHAs can help assess global hemostasis but may be affected by circuit anticoagulation[73]
  3. Combined circuit strategies: Patients requiring multiple extracorporeal therapies (e.g., ECMO plus CRRT) present complex anticoagulation challenges often requiring individualized protocols and multidisciplinary input.[74]

Massive Transfusion and Blood Conservation

Massive transfusion, defined as replacement of >50% of blood volume within 3 hours or >10 units of PRBCs in 24 hours, requires coordinated resuscitation to avoid worsening coagulopathy:[75]

  1. Balanced component therapy: Targeting ratios approximating whole blood (PRBC:FFP:platelets of 1:1:1) improves outcomes compared to PRBC-predominant strategies in traumatic hemorrhage, though evidence specifically in medical patients is more limited.[76]

  2. Hemostatic resuscitation: Early administration of tranexamic acid (within 3 hours of bleeding onset), fibrinogen supplementation, and factor concentrates may reduce total blood product requirements.[77]

  3. Blood conservation strategies:

    • Restrictive transfusion thresholds (Hb 7 g/dL for most critically ill patients)
    • Minimizing phlebotomy volume and frequency
    • Cell salvage techniques when appropriate
    • Microsampling technologies for laboratory testing[78]
  4. Hypocalcemia prevention: Massive transfusion of citrated blood products causes calcium chelation. Ionized calcium should be monitored and supplemented to maintain levels >1.0 mmol/L.[79]

Thromboprophylaxis in Complex MICU Patients

Critically ill medical patients face competing bleeding and thrombotic risks, requiring nuanced thromboprophylaxis approaches:[80]

  1. Risk stratification: Tools such as the IMPROVE VTE and IMPROVE Bleeding Risk Scores help balance competing risks, though their validation in diverse ICU populations remains incomplete.[81]

  2. Mechanical prophylaxis: Sequential compression devices provide some protection when pharmacologic prophylaxis is contraindicated but are less effective as monotherapy.[82]

  3. Special populations:

    • Obesity: Consider weight-based dosing or anti-Xa monitoring
    • Renal dysfunction: Avoid LMWH with GFR <30 mL/min or use with anti-Xa monitoring
    • Liver dysfunction: Standard prophylaxis can generally be used despite elevated INR if platelet count >50,000/μL[83]
  4. Duration considerations: Extended thromboprophylaxis post-discharge should be considered for high-risk patients, particularly with COVID-19, active cancer, or persistent immobility.[84]

Future Directions

The field of critical illness-associated coagulopathy continues to evolve rapidly, with several promising areas of investigation:

  1. Precision diagnostics:

    • Thrombin generation assays and other global coagulation tests may provide more comprehensive hemostatic assessment.[85]
    • Machine learning algorithms integrating multiple biomarkers show promise for personalized risk stratification.[86]
    • Point-of-care molecular testing may allow rapid identification of genetic polymorphisms affecting coagulation and drug metabolism.[87]
  2. Targeted therapeutics:

    • NET-targeting therapies including DNase and neutrophil inhibitors are being investigated for thromboinflammatory conditions.[88]
    • Novel anticoagulants with reduced bleeding risk through selective factor inhibition or context-sensitive activation.[89]
    • Engineered proteins combining anticoagulant and cytoprotective properties, such as modified thrombomodulin variants.[90]
  3. Personalized approaches:

    • Pharmacogenomic-guided anticoagulation may optimize efficacy while minimizing bleeding risk.[91]
    • Host response patterns may allow identification of patient subpopulations most likely to benefit from specific interventions.[92]
    • Integration of omics data with clinical parameters to create precision medicine algorithms for coagulopathy management.[93]

Conclusion

Coagulopathy in the medical ICU represents a complex, dynamic process requiring integrated understanding of modern hemostatic principles. By moving beyond the traditional dichotomy of "bleeding versus clotting" toward a nuanced appreciation of simultaneous dysregulation across multiple hemostatic pathways, clinicians can develop more effective diagnostic and management strategies. The emergence of COVID-19-associated coagulopathy has accelerated research in this field, highlighting the interconnections between inflammation, endothelial dysfunction, and coagulation.

Optimal management requires:

  1. Recognition of the dynamic nature of critical illness-associated coagulopathy
  2. Integration of clinical assessment with conventional and advanced laboratory testing
  3. Individualized approaches considering specific underlying conditions
  4. Balance between thrombotic and bleeding risks
  5. Targeted interventions addressing specific hemostatic derangements

As our understanding evolves, management will increasingly shift from reactive correction of laboratory abnormalities toward proactive, pathway-specific interventions guided by comprehensive hemostatic assessment. This approach promises to improve outcomes in this challenging aspect of critical care medicine.

References

  1. Levi M, Opal SM. Coagulation abnormalities in critically ill patients. Crit Care. 2006;10(4):222. doi:10.1186/cc4975

  2. Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014;370(9):847-859. doi:10.1056/NEJMra1208626

  3. Simmons J, Pittet JF. The coagulopathy of acute sepsis. Curr Opin Anaesthesiol. 2015;28(2):227-236. doi:10.1097/ACO.0000000000000163

  4. Hoffman M, Monroe DM. A cell-based model of hemostasis. Thromb Haemost. 2001;85(6):958-965. doi:10.1055/s-0037-1615947

  5. Iba T, Levy JH. Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis. J Thromb Haemost. 2018;16(2):231-241. doi:10.1111/jth.13911

  6. Crowther MA, Cook DJ, Meade MO, et al. Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors. J Crit Care. 2005;20(4):348-353. doi:10.1016/j.jcrc.2005.09.008

  7. Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033-2040. doi:10.1182/blood.2020006000

  8. Monroe DM, Hoffman M. What does it take to make the perfect clot? Arterioscler Thromb Vasc Biol. 2006;26(1):41-48. doi:10.1161/01.ATV.0000193624.28251.83

  9. Smith SA, Travers RJ, Morrissey JH. How it all starts: Initiation of the clotting cascade. Crit Rev Biochem Mol Biol. 2015;50(4):326-336. doi:10.3109/10409238.2015.1050550

  10. Iba T, Levy JH. Derangement of the endothelial glycocalyx in sepsis. J Thromb Haemost. 2019;17(2):283-294. doi:10.1111/jth.14371

  11. Zarychanski R, Houston DS. Assessing thrombocytopenia in the intensive care unit: the past, present, and future. Hematology Am Soc Hematol Educ Program. 2017;2017(1):660-666. doi:10.1182/asheducation-2017.1.660

  12. Thomas MR, Storey RF. The role of platelets in inflammation. Thromb Haemost. 2015;114(3):449-458. doi:10.1160/TH14-12-1067

  13. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers. 2016;2:16037. doi:10.1038/nrdp.2016.37

  14. Moore HB, Moore EE, Liras IN, et al. Acute fibrinolysis shutdown after injury occurs frequently and increases mortality: a multicenter evaluation of 2,540 severely injured patients. J Am Coll Surg. 2016;222(4):347-355. doi:10.1016/j.jamcollsurg.2016.01.006

  15. Esmon CT. The interactions between inflammation and coagulation. Br J Haematol. 2005;131(4):417-430. doi:10.1111/j.1365-2141.2005.05753.x

  16. Foley JH, Conway EM. Cross talk pathways between coagulation and inflammation. Circ Res. 2016;118(9):1392-1408. doi:10.1161/CIRCRESAHA.116.306853

  17. Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019;133(9):906-918. doi:10.1182/blood-2018-11-882993

  18. Stouthard JM, Levi M, Hack CE, et al. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost. 1996;76(5):738-742. doi:10.1055/s-0038-1650653

  19. Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood. 2014;123(18):2768-2776. doi:10.1182/blood-2013-10-463646

  20. McDonald B, Davis RP, Kim SJ, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017;129(10):1357-1367. doi:10.1182/blood-2016-09-741298

  21. Markiewski MM, Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD. Complement and coagulation: strangers or partners in crime? Trends Immunol. 2007;28(4):184-192. doi:10.1016/j.it.2007.02.006

  22. Dahlbäck B. Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases. J Intern Med. 2005;257(3):209-223. doi:10.1111/j.1365-2796.2004.01444.x

  23. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86(5):1327-1330. doi:10.1055/s-0037-1616068

  24. Iba T, Levy JH, Warkentin TE, et al. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989-1994. doi:10.1111/jth.14578

  25. Iba T, Levy JH, Connors JM, Warkentin TE, Thachil J, Levi M. The unique characteristics of COVID-19 coagulopathy. Crit Care. 2020;24(1):360. doi:10.1186/s13054-020-03077-0

  26. Semeraro N, Ammollo CT, Semeraro F, Colucci M. Sepsis-associated disseminated intravascular coagulation and thromboembolic disease. Mediterr J Hematol Infect Dis. 2010;2(3):e2010024. doi:10.4084/MJHID.2010.024

  27. Harahsheh Y, Ho KM. Use of viscoelastic tests to predict clinical thromboembolic events: A systematic review and meta-analysis. Eur J Haematol. 2018;100(2):113-123. doi:10.1111/ejh.12992

  28. Segal JB, Dzik WH; Transfusion Medicine/Hemostasis Clinical Trials Network. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: a systematic review. Transfusion. 2005;45(9):1413-1425. doi:10.1111/j.1537-2995.2005.00546.x

  29. Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol. 2014;89(2):228-232. doi:10.1002/ajh.23599

  30. Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev. 2012;26(1):1-13. doi:10.1016/j.tmrv.2011.07.005

  31. Müller MC, Meijers JC, Vroom MB, Juffermans NP. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care. 2014;18(1):R30. doi:10.1186/cc13721

  32. Veigas PV, Callum J, Rizoli S, Nascimento B, da Luz LT. A systematic review on the rotational thrombelastometry (ROTEM) values for the diagnosis of coagulopathy, prediction and guidance of blood transfusion and prediction of mortality in trauma patients. Scand J Trauma Resusc Emerg Med. 2016;24(1):114. doi:10.1186/s13049-016-0308-2

  33. Toh CH, Hoots WK; SSC on Disseminated Intravascular Coagulation of the ISTH. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost. 2007;5(3):604-606. doi:10.1111/j.1538-7836.2007.02313.x

  34. Koyama K, Madoiwa S, Nunomiya S, et al. Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study. Crit Care. 2014;18(1):R13. doi:10.1186/cc13190

  35. Fuchs TA, Brill A, Duerschmied D, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A. 2010;107(36):15880-15885. doi:10.1073/pnas.1005743107

  36. Walsh M, Moore EE, Moore HB, et al. Use of viscoelastography in malignancy-associated coagulopathy and thrombosis: a review. Semin Thromb Hemost. 2019;45(4):354-372. doi:10.1055/s-0039-1687890

  37. Iba T, Nisio MD, Levy JH, Kitamura N, Thachil J. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017;7(9):e017046. doi:10.1136/bmjopen-2017-017046

  38. Warren BL, Eid A, Singer P, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 2001;286(15):1869-1878. doi:10.1001/jama.286.15.1869

  39. Wikkelsø A, Wetterslev J, Møller AM, Afshari A. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding. Cochrane Database Syst Rev. 2016;2016(8):CD007871. doi:10.1002/14651858.CD007871.pub3

  40. Deng Y, He L, Yang J, Wang J. Serum antithrombin III and D-dimer levels as potential biomarkers for early sepsis-induced coagulopathy. Clin Lab. 2020;66(12). doi:10.7754/Clin.Lab.2020.200414

  41. Vincent JL, Francois B, Zabolotskikh I, et al. Effect of a recombinant human soluble thrombomodulin on mortality in patients with sepsis-associated coagulopathy: the SCARLET randomized clinical trial. JAMA. 2019;321(20):1993-2002. doi:10.1001/jama.2019.5358

  42. Allingstrup M, Wetterslev J, Ravn FB, Møller AM, Afshari A. Antithrombin III for critically ill patients. Cochrane Database Syst Rev. 2016;2016(2):CD005370. doi:10.1002/14651858.CD005370.pub3

  43. Porto BN, Stein RT. Neutrophil extracellular traps in pulmonary diseases: too much of a good thing? Front Immunol. 2016;7:311. doi:10.3389/fimmu.2016.00311

  44. Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-1098. doi:10.1007/s00134-020-06062-x

  45. Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID-19. J Thromb Haemost. 2020;18(9):2103-2109. doi:10.1111/jth.14975

  46. ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators, et al. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N Engl J Med. 2021;385(9):790-802. doi:10.1056/NEJMoa2105911

  47. Chow JH, Khanna AK, Kethireddy S, et al. Aspirin use is associated with decreased mechanical ventilation, intensive care unit admission, and in-hospital mortality in hospitalized patients with coronavirus disease 2019. Anesth Analg. 2021;132(4):930-941. doi:10.1213/ANE.0000000000005292

  48. Spyropoulos AC, Levy JH, Ageno W, et al. Scientific and Standardization Committee communication: Clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020;18(8):1859-1865. doi:10.1111/jth.14929

  49. Extracorporeal Life Support Organization (ELSO): ELSO COVID-19 Interim Guidelines - ECMO for COVID-19 patients with severe cardiopulmonary failure. 2020. Available at: https://www.elso.org/Portals/0/Files/pdf/ELSO%20COVID%20Guidelines%20-%20May%202020.pdf. Accessed January 15, 2025.

  50. Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood. 2010;116(6):878-885. doi:10.1182/blood-2010-02-261891

  51. Mallett SV. Clinical utility of viscoelastic tests of coagulation (TEG/ROTEM) in patients with liver disease and during liver transplantation. Semin Thromb Hemost. 2015;41(5):527-537. doi:10.1055/s-0035-1550434

  52. De Pietri L, Bianchini M, Montalti R, et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial. Hepatology. 2016;63(2):566-573. doi:10.1002/hep.28148

  53. Intagliata NM, Argo CK, Stine JG, Lisman T, Caldwell SH, Violi F; Faculty of the 7th International Coagulation in Liver Disease Conference. Concepts and controversies in haemostasis and thrombosis associated with liver disease: Proceedings of the 7th International Coagulation in Liver Disease Conference. Thromb Haemost. 2018;118(8):1491-1506. doi:10.1055/s-0038-1666861

  54. Senzolo M, Sartori MT, Lisman T. Should we give thromboprophylaxis to patients with liver cirrhosis and coagulopathy? HPB (Oxford). 2009;11(6):459-464. doi:10.1111/j.1477-2574.2009.00079.x

  55. Drolz A, Horvatits T, Roedl K, et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis. Hepatology. 2016;64(2):556-568. doi:10.1002/hep.28628

  56. Escolar G, Díaz-Ricart M, Cases A. Uremic platelet dysfunction: past and present. Curr Hematol Rep. 2005;4(5):359-367.

  57. Kaw D, Malhotra D. Platelet dysfunction and end-stage renal disease. Semin Dial. 2006;19(4):317-322. doi:10.1111/j.1525-139X.2006.00179.x

  58. Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood. 1997;90(7):2515-2521. doi:10.1182/blood.V90.7.2515

  59. Livio M, Mannucci PM, Viganò G, et al. Conjugated estrogens for the management of bleeding associated with renal failure. N Engl J Med. 1986;315(12):731-735. doi:10.1056/NEJM198609183151204

  60. Valeri CR, Cassidy G, Pivacek LE, et al. Anemia-induced increase in the bleeding time: implications for treatment of nonsurgical blood loss. Transfusion. 2001;41(8):977-983. doi:10.1046/j.1537-2995.2001.41080977.x

  61. Grand'Maison A, Charest AF, Geerts WH. Anticoagulant use in patients with chronic renal impairment. Am J Cardiovasc Drugs. 2005;5(5):291-305. doi:10.2165/00129784-200505050-00002

  62. Sié P. Spotlight on drug-induced coagulation disorders. Drugs. 2020;80(3):251-253. doi:10.1007/s40265-020-01260-9

  63. Pollack CV Jr, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal - full cohort analysis. N Engl J Med. 2017;377(5):431-441. doi:10.1056/NEJMoa1707278

  64. Connolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019;380(14):1326-1335. doi:10.1056/NEJMoa1814051

  65. Schulman S, Gross PL, Ritchie B, et al. Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Thromb Haemost. 2018;118(5):842-851. doi:10.1055/s-0038-1636541

  66. Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest. 2001;119(1 Suppl):64S-94S. doi:10.1378/chest.119.1_suppl.64s

  67. Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-based ticagrelor reversal agent in healthy volunteers. N Engl J Med. 2019;380(19):1825-1833. doi:10.1056/NEJMoa1901778

  68. Al-Samkari H, Karp Leaf RS, Dzik WH, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489-500. doi:10.1182/blood.2020006520

  69. Ghaswalla PK, Harpe SE, Tassone D, Slattum PW. Warfarin-antibiotic interactions in older adults of an outpatient anticoagulation clinic. Am J Geriatr Pharmacother. 2012;10(6):352-360. doi:10.1016/j.amjopharm.2012.09.006

  70. Brophy PD, Somers MJ, Baum MA, et al. Multi-centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT). Nephrol Dial Transplant. 2005;20(7):1416-1421. doi:10.1093/ndt/gfh817

  71. Esper SA, Levy JH, Waters JH, Welsby IJ. Extracorporeal membrane oxygenation in the adult: a review of anticoagulation monitoring and transfusion. Anesth Analg. 2014;118(4):731-743. doi:10.1213/ANE.0000000000000115

  72. Oudemans-van Straaten HM, Bosman RJ, Koopmans M, et al. Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med. 2009;37(2):545-552. doi:10.1097/CCM.0b013e3181953c5e

  73. Koster A, Fischer T, Praus M, et al. Hemostatic activation and inflammatory response during cardiopulmonary bypass: impact of heparin management. Anesthesiology. 2002;97(4):837-841. doi:10.1097/00000542-200210000-00014

  74. Protti A, L'Acqua C, Panigada M. The delicate balance between pro-(risk of thrombosis) and anti-(risk of bleeding) coagulation during extracorporeal membrane oxygenation. Ann Transl Med. 2016;4(7):139. doi:10.21037/atm.2016.03.06

  75. Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471-482. doi:10.1001/jama.2015.12

  76. Innerhofer P, Fries D, Mittermayr M, et al. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol. 2017;4(6):e258-e271. doi:10.1016/S2352-3026(17)30077-7

  77. CRASH-2 trial collaborators, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. doi:10.1016/S0140-6736(10)60835-5

  78. Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002;288(12):1499-1507. doi:10.1001/jama.288.12.1499

  79. Giancarelli A, Birrer KL, Alban RF, Hobbs BP, Liu-DeRyke X. Hypocalcemia in trauma patients receiving massive transfusion. J Surg Res. 2016;202(1):182-187. doi:10.1016/j.jss.2015.12.036

  80. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e195S-e226S. doi:10.1378/chest.11-2296

  81. Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. doi:10.1378/chest.09-3081

  82. Ho KM, Tan JA. Stratified meta-analysis of intermittent pneumatic compression of the lower limbs to prevent venous thromboembolism in hospitalized patients. Circulation. 2013;128(9):1003-1020. doi:10.1161/CIRCULATIONAHA.113.002690

  83. Spyropoulos AC. Emerging strategies in the prevention of venous thromboembolism in hospitalized medical patients. Chest. 2005;128(2):958-969. doi:10.1378/chest.128.2.958

  84. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375(6):534-544. doi:10.1056/NEJMoa1601747

  85. Tripodi A. Thrombin generation assay and its application in the clinical laboratory. Clin Chem. 2016;62(5):699-707. doi:10.1373/clinchem.2015.248625

  86. Fröhlich M, Lefering R, Probst C, et al. Epidemiology and risk factors of multiple-organ failure after multiple trauma: an analysis of 31,154 patients from the TraumaRegister DGU. J Trauma Acute Care Surg. 2014;76(4):921-927. doi:10.1097/TA.0000000000000199

  87. Kimmel SE, French B, Kasner SE, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013;369(24):2283-2293. doi:10.1056/NEJMoa1310669

  88. Jorch SK, Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat Med. 2017;23(3):279-287. doi:10.1038/nm.4294

  89. Wong PC, Pinto DJ, Zhang D. Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor. J Thromb Thrombolysis. 2011;31(4):478-492. doi:10.1007/s11239-011-0551-3

  90. Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood. 2007;109(8):3161-3172. doi:10.1182/blood-2006-09-003004

  91. Pirmohamed M, Burnside G, Eriksson N, et al. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013;369(24):2294-2303. doi:10.1056/NEJMoa1311386

  92. Shapiro NI, Schuetz P, Yano K, et al. The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis. Crit Care. 2010;14(5):R182. doi:10.1186/cc9290

  93. Davenport EE, Burnham KL, Radhakrishnan J, et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016;4(4):259-271. doi:10.1016/S2213-2600(16)00046-1

VAP Prevention Bundles

 Ventilator-Associated Pneumonia Prevention Bundles: A Practical Guide for Critical Care Residents

Dr Neeraj Manikath, claude.ai

Abstract

Ventilator-associated pneumonia (VAP) remains a significant complication in mechanically ventilated patients, associated with increased morbidity, mortality, and healthcare costs. Prevention bundles comprising evidence-based interventions have demonstrated effectiveness in reducing VAP rates. This review provides a comprehensive overview of VAP pathophysiology, bundle components with their supporting evidence, implementation challenges, and practical strategies for successful adoption in intensive care settings. A case-based approach illustrates real-world application of these principles. Understanding and implementing VAP prevention bundles represents an essential skill for critical care residents, with potential to significantly improve patient outcomes.

Keywords: Ventilator-associated pneumonia, prevention bundles, critical care, mechanical ventilation, implementation, quality improvement

Introduction

Despite advances in critical care medicine, ventilator-associated pneumonia (VAP) continues to be one of the most common healthcare-associated infections in the intensive care unit (ICU). With attributable mortality rates of 13-55% and significant increases in length of stay and healthcare costs, VAP prevention represents a critical quality improvement target (Safdar et al., 2005; Melsen et al., 2013). Prevention bundles—groupings of evidence-based interventions implemented together—have demonstrated significant reductions in VAP rates when applied consistently. This review provides critical care residents with practical guidance on understanding, implementing, and troubleshooting VAP prevention bundles in daily practice.

Defining Ventilator-Associated Pneumonia

Diagnostic Criteria and Challenges

VAP is defined as pneumonia that develops 48 hours or more after endotracheal intubation in mechanically ventilated patients (Kalil et al., 2016). The Centers for Disease Control and Prevention (CDC) has introduced surveillance definitions for ventilator-associated events (VAE), which include:

Ventilator-Associated Condition (VAC)

Infection-related Ventilator-Associated Complication (IVAC)

Possible and Probable VAP

These definitions focus on objective criteria including worsening oxygenation following a period of stability, signs of infection, and microbiological evidence (CDC, 2021). However, clinical diagnosis remains challenging due to the overlap with other conditions affecting critically ill patients.

Pathophysiology and Risk Factors

VAP develops through several pathophysiological mechanisms:

Aspiration of oropharyngeal secretions: The endotracheal tube (ET) bypasses natural defense mechanisms, allowing microaspiration of colonized secretions

Biofilm formation: Bacterial biofilms develop on the ET surface, providing a reservoir for respiratory pathogens

Microaspiration around the ET cuff: Despite inflation, microchannels allow passage of subglottic secretions

Impaired mucociliary clearance: Mechanical ventilation and underlying conditions impair normal clearance mechanisms

Clinical Pearl: The transition from oropharyngeal colonization to tracheobronchial colonization to VAP is a continuum. Interventions targeting any stage of this progression may reduce VAP incidence.

Risk factors for VAP include:

Patient-related: Advanced age, immunosuppression, malnutrition, chronic lung disease, ARDS

Intervention-related: Duration of mechanical ventilation, reintubation, supine positioning, gastric overdistention

Healthcare-related: Hand hygiene compliance, ICU staffing ratios, failure to adhere to prevention protocols

Components of VAP Prevention Bundles

Evolution of VAP Bundles

VAP prevention bundles have evolved over time. The Institute for Healthcare Improvement (IHI) initially promoted a five-element bundle, which has been modified and expanded based on emerging evidence. Current bundles incorporate interventions targeting multiple pathophysiological mechanisms of VAP development (Klompas et al., 2014).

Evidence-Based Bundle Components

1. Elevation of the Head of Bed (HOB)

Recommendation: Maintain HOB elevation at 30-45 degrees unless contraindicated

Evidence: Drakulovic et al. (1999) demonstrated in a randomized controlled trial that semi-recumbent positioning (45 degrees) compared to supine positioning (0 degrees) reduced the incidence of clinically suspected and microbiologically confirmed VAP (8% vs. 34%, p=0.003)

Mechanism: Reduces gastroesophageal reflux and aspiration of gastric contents

Clinical Pearl: Use bed angle indicators to confirm proper elevation. When strict HOB elevation is contraindicated, aim for the highest angle clinically permissible, as even modest elevation provides benefit over completely supine positioning.

2. Daily Sedation Interruption and Spontaneous Breathing Trials (SBTs)

Recommendation: Perform daily assessment of readiness to extubate with coordinated sedation interruption and SBTs

Evidence: Girard et al. (2008) demonstrated in the Awakening and Breathing Controlled (ABC) trial that paired sedation interruption and SBTs resulted in more ventilator-free days (14.7 vs. 11.6 days, p<0.001) and reduced durations of mechanical ventilation

Mechanism: Minimizes duration of mechanical ventilation, the primary risk factor for VAP

Clinical Pearl: Implement a standardized protocol linking sedation interruption with SBTs to overcome the common barrier of uncoordinated sedation and ventilator management.

3. Oral Care with Chlorhexidine

Recommendation: Provide oral care with chlorhexidine (0.12-2% concentration) at least twice daily

Evidence: A meta-analysis by Hua et al. (2016) showed that chlorhexidine reduced the risk of VAP compared with placebo (RR 0.74, 95% CI 0.61-0.89), with stronger effects in cardiac surgery patients

Mechanism: Reduces oropharyngeal colonization with pathogenic bacteria

Clinical Pearl: Recent evidence suggests potential mortality concerns with chlorhexidine in non-cardiac surgery patients. Consider using lower concentrations (0.12-0.2%) for general ICU patients, while maintaining rigorous mechanical oral care.

4. Subglottic Secretion Drainage (SSD)

Recommendation: Use endotracheal tubes with subglottic secretion drainage ports for patients anticipated to require >48-72 hours of mechanical ventilation

Evidence: A meta-analysis by Mao et al. (2016) demonstrated that SSD reduced VAP incidence (RR 0.55, 95% CI 0.46-0.66) without affecting duration of mechanical ventilation or mortality

Mechanism: Prevents microaspiration of pooled secretions above the endotracheal tube cuff

Clinical Pearl: Ensure proper functioning of SSD by flushing the lumen with air or saline if secretions are not being retrieved. Consider continuous versus intermittent suctioning based on secretion viscosity.

5. Endotracheal Tube Cuff Pressure Management

Recommendation: Maintain endotracheal tube cuff pressure between 20-30 cmH₂O with regular monitoring

Evidence: Nseir et al. (2011) demonstrated that continuous control of cuff pressure reduced microaspiration of gastric contents and tracheobronchial colonization

Mechanism: Prevents microaspiration around the cuff while avoiding tracheal mucosal damage from excessive pressure

Clinical Pearl: Temperature changes, patient position, and suctioning can all affect cuff pressure. Implement a protocol for regular monitoring (at least every 8 hours) and adjustment.

6. Early Mobility

Recommendation: Implement progressive mobility protocols for all eligible patients

Evidence: Schweickert et al. (2009) demonstrated that early physical and occupational therapy during daily sedation interruption reduced delirium duration and improved functional outcomes

Mechanism: Reduces atelectasis, improves respiratory mechanics, and shortens duration of mechanical ventilation

Clinical Pearl: Even passive range of motion and in-bed exercises provide benefit. Use a stepwise approach to mobility progression based on patient tolerance and stability.

7. Stress Ulcer Prophylaxis and Enteral Nutrition Management

Recommendation: Provide stress ulcer prophylaxis only when indicated; initiate early enteral nutrition with proper positioning and gastric residual volume monitoring

Evidence: Meta-analyses show that overly aggressive acid suppression may increase pneumonia risk through gastric colonization (Alhazzani et al., 2018)

Mechanism: Balances the competing risks of stress ulceration versus gastric colonization and aspiration

Clinical Pearl: Consider risk-benefit of acid suppression for each patient. When enteral nutrition is established, assess continued need for stress ulcer prophylaxis.

8. Hand Hygiene and Standard Precautions

Recommendation: Strict adherence to hand hygiene before and after patient contact and with ventilator circuit manipulation

Evidence: Hand hygiene is a cornerstone of infection prevention with substantial evidence supporting its role in reducing healthcare-associated infections (Allegranzi & Pittet, 2009)

Mechanism: Prevents cross-contamination between patients and equipment

Clinical Pearl: Place alcohol-based hand rub at the bedside and ventilator stations to improve compliance. Consider using visual cues for hand hygiene before ventilator manipulation.

Implementation Challenges and Solutions

Common Barriers to Bundle Implementation

Despite strong evidence supporting individual components, bundle implementation faces multiple barriers:

Knowledge gaps: Lack of awareness of bundle components or their rationale

Resource constraints: Inadequate staffing, equipment, or time

Behavioral factors: Resistance to change, lack of buy-in from staff

Coordination challenges: Lack of clear responsibility assignment

Monitoring difficulties: Inconsistent surveillance and feedback

Implementation Strategies

1. Education and Training

Multidisciplinary education sessions on VAP pathophysiology and prevention

Simulation-based training for technical aspects (e.g., proper positioning, oral care techniques)

Case-based learning using real VAP events as teaching opportunities

2. System Redesign

Standardized order sets incorporating all bundle elements

Visual cues (e.g., bedside cards, EMR alerts) to remind staff of bundle components

Documentation tools integrated into daily workflows

Equipment modifications (e.g., HOB angle indicators, automated cuff pressure monitors)

3. Culture Change

Engage opinion leaders and champions across disciplines

Celebrate successes and recognize high-performing teams

Frame VAP prevention as a patient safety priority rather than a regulatory requirement

Develop shared accountability across physician, nursing, and respiratory therapy teams

4. Measurement and Feedback

Regular surveillance of process measures (bundle compliance) and outcomes (VAP rates)

Unit-level dashboards with transparent reporting of performance

Just-in-time feedback for missed opportunities

Root cause analysis of VAP cases to identify system failures

Clinical Pearl: The most successful implementation approaches address multiple barriers simultaneously through what's known as a "multimodal strategy." Single interventions rarely achieve sustained improvement.

Case Example: Applying VAP Prevention Principles

Clinical Scenario

Mr. J is a 67-year-old male with COPD admitted to the ICU with severe community-acquired pneumonia and respiratory failure requiring intubation. His course is complicated by shock requiring vasopressors and acute kidney injury. By day 3, his hemodynamics have stabilized, but he remains on moderate ventilatory support (FiO₂ 0.5, PEEP 8 cmH₂O).

Application of VAP Bundle

Morning ICU Rounds (Day 3)

Assessment:

Current sedation: Propofol infusion at 30 mcg/kg/min

Ventilator settings: AC/VC, RR 14, TV 450 mL, FiO₂ 0.5, PEEP 8 cmH₂O

Patient positioned at 20-degree elevation due to concern for pressure injury

Last oral care documented 10 hours ago

Endotracheal tube: Standard tube without subglottic suctioning

Cuff pressure last checked 12 hours ago

Minimal spontaneous movement, Richmond Agitation-Sedation Scale (RASS) -3

Receiving enteral nutrition at 40 mL/hr with pantoprazole for stress ulcer prophylaxis

Bundle Implementation:

Head of Bed Elevation

Increase HOB to 30 degrees

Implement pressure redistribution mattress to address pressure injury concerns

Document contraindications to 45-degree elevation in daily goals

Sedation and SBT

Decrease propofol to target RASS -1 to 0

Schedule coordinated sedation interruption and SBT for 10:00 AM

Document SBT parameters and failure criteria

Oral Care

Perform comprehensive oral assessment

Implement q4h oral care with chlorhexidine

Document in oral care flowsheet

Subglottic Secretion Management

Unable to replace ET with SSD tube at this time

Ensure meticulous above-the-cuff suctioning with oral care

Consider tube exchange if prolonged ventilation anticipated beyond 5-7 days

Cuff Pressure Management

Measure cuff pressure: found to be 15 cmH₂O

Adjust to 25 cmH₂O

Implement q8h cuff pressure checks

Early Mobility

Physical therapy consultation for assessment

Begin passive range of motion with next sedation interruption

Develop progressive mobility plan

Nutrition and Stress Ulcer Prophylaxis

Continue enteral nutrition

Reassess need for pantoprazole given enteral feeding

Monitor gastric residuals q4h

Hand Hygiene and Standard Precautions

Hand hygiene audit during rounds

Reinforce ventilator circuit care practices

Ensure appropriate glove and gown use

Patient Outcome

By day 5, Mr. J successfully completed a 2-hour SBT and was extubated to high-flow nasal cannula. He did not develop VAP during his ICU stay. The implementation of the full prevention bundle, particularly the coordinated sedation interruption and SBT, facilitated early extubation despite his risk factors for prolonged ventilation.

Key Points for Residents to Remember

Prevention is paramount: VAP is easier to prevent than treat, with each day of mechanical ventilation increasing risk. Focus on daily assessment of extubation readiness.

Bundle compliance matters: The synergistic effect of all components exceeds individual interventions. A gap in any component reduces the overall effectiveness of the bundle.

Implementation science is critical: Understanding barriers and facilitators to bundle implementation is as important as knowing the evidence behind each component.

Multidisciplinary approach: VAP prevention requires collaboration between physicians, nurses, respiratory therapists, physical therapists, and pharmacists. Engage the entire team in prevention efforts.

Measurement drives improvement: Regular feedback on both process measures (bundle compliance) and outcomes (VAP rates) motivates continued attention to prevention.

Conclusion

VAP prevention bundles represent a cornerstone of quality and safety in critical care. While individual components have evolved over time, the principle of implementing multiple evidence-based interventions simultaneously remains constant. For critical care residents, mastering VAP prevention requires not only understanding the pathophysiology and evidence, but also developing skills in implementation science and quality improvement. By applying these principles consistently, residents can significantly impact patient outcomes while developing essential quality improvement competencies for their future practice.

References

1.Alhazzani W, Alshamsi F, Belley-Cote E, et al. Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med. 2018;44(1):1-11.

2.Allegranzi B, Pittet D. Role of hand hygiene in healthcare-associated infection prevention. J Hosp Infect. 2009;73(4):305-315.

3.Centers for Disease Control and Prevention. Ventilator-Associated Event (VAE) Protocol. 2021. Available at: https://www.cdc.gov/nhsn/pdfs/pscmanual/10-vae_final.pdf

4.Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogué S, Ferrer M. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet. 1999;354(9193):1851-1858.

5.Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126-134.

6.Hua F, Xie H, Worthington HV, Furness S, Zhang Q, Li C. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev. 2016;10:CD008367.

7.Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111.

8.Klompas M, Branson R, Eichenwald EC, et al. Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(8):915-936.

9.Mao Z, Gao L, Wang G, et al. Subglottic secretion suction for preventing ventilator-associated pneumonia: an updated meta-analysis and trial sequential analysis. Crit Care. 2016;20(1):353.

10.Melsen WG, Rovers MM, Groenwold RH, et al. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis. 2013;13(8):665-671.

11.Nseir S, Zerimech F, Fournier C, et al. Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients. Am J Respir Crit Care Med. 2011;184(9):1041-1047.

12.Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005;33(10):2184-2193.

13.Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009;373(9678):1874-1882.

14.Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis. 2011;11(11):845-854.

15Muscedere J, Rewa O, McKechnie K, Jiang X, Laporta D, Heyland DK. Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis. Crit Care Med. 2011;39(8):1985-1991.

16.Klompas M, Li L, Kleinman K, Szumita PM, Massaro AF. Associations between ventilator bundle components and outcomes. JAMA Intern Med. 2016;176(9):1277-1283.

17.Magill SS, O'Leary E, Janelle SJ, et al. Changes in prevalence of health care-associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-1744.

18.Bouadma L, Klompas M, Sudom K, et al. Ventilator-associated pneumonia in adult intensive care units: a systematic review and network meta-analysis. Intensive Care Med. 2022;48(3):317-327.

19.Lacherade JC, De Jonghe B, Guezennec P, et al. Intermittent subglottic secretion drainage and ventilator-associated pneumonia: a multicenter trial. Am J Respir Crit Care Med. 2010;182(7):910-917.

20.Li Bassi G, Senussi T, Aguilera Xiol E. Prevention of ventilator-associated pneumonia. Curr Opin Infect Dis. 2017;30(2):214-220.

21.American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416.

22.Wang L, Li X, Yang Z, et al. Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation. Cochrane Database Syst Rev. 2016;(1):CD009946.

23.Guterres da Silva SJ, Ventura da Silva TB, et al. Bundle adherence and ventilator-associated pneumonia: a multicenter observational study. Crit Care Med. 2020;48(8):1162-1169.

24.Ferrer R, Artigas A. Clinical review: Non-antibiotic strategies for preventing ventilator-associated pneumonia. Crit Care. 2022;26(1):100.

25.Timsit JF, Esaied W, Neuville M, Bouadma L, Mourvillier B. Update on ventilator-associated pneumonia. F1000Res. 2017;6:2061.

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