Monday, July 21, 2025

Therapeutic Hypothermia in Non-Cardiac Arrest Conditions

 

Therapeutic Hypothermia in Non-Cardiac Arrest Conditions: Expanding Horizons Beyond Post-Cardiac Arrest Care

Dr Neeraj Manikath , claude.ai

Abstract

Background: While therapeutic hypothermia has established efficacy in post-cardiac arrest neuroprotection, its application in other critical care conditions remains an evolving frontier. This review examines the evidence, mechanisms, and practical considerations for therapeutic hypothermia in traumatic brain injury, hepatic encephalopathy, and refractory status epilepticus.

Methods: Systematic review of literature from 2010-2024 focusing on therapeutic hypothermia applications beyond cardiac arrest, with emphasis on pathophysiological mechanisms, clinical outcomes, and practical implementation strategies.

Results: Emerging evidence supports selective use of therapeutic hypothermia in specific non-cardiac arrest conditions, though optimal protocols and patient selection criteria continue to evolve. Success depends critically on precise temperature management, comprehensive monitoring, and anticipation of complications.

Conclusions: Therapeutic hypothermia represents a promising adjunctive therapy in selected non-cardiac arrest conditions when implemented with rigorous protocols and appropriate patient selection. Future research should focus on personalized cooling strategies and biomarker-guided therapy.

Keywords: Therapeutic hypothermia, traumatic brain injury, hepatic encephalopathy, status epilepticus, targeted temperature management, neuroprotection


Introduction

The concept of therapeutic hypothermia has evolved from an experimental intervention to an evidence-based therapy in post-cardiac arrest care. However, the neuroprotective and metabolic benefits of controlled cooling extend beyond this established indication. The pathophysiological rationale for hypothermia—reduced cerebral metabolic demand, decreased inflammatory cascade activation, and stabilization of cellular membranes—applies to various critical care conditions characterized by brain injury and metabolic dysregulation.

This review examines the current evidence and practical considerations for therapeutic hypothermia in three key non-cardiac arrest conditions: traumatic brain injury (TBI), hepatic encephalopathy, and refractory status epilepticus. Understanding both the potential benefits and implementation challenges is crucial for critical care practitioners considering this intervention.


Pathophysiological Mechanisms of Therapeutic Hypothermia

Primary Neuroprotective Mechanisms

Therapeutic hypothermia exerts neuroprotection through multiple interconnected pathways. Temperature reduction of 1-3°C decreases cerebral metabolic rate by approximately 6-10% per degree Celsius, reducing oxygen and glucose consumption during periods of compromised perfusion. This metabolic suppression provides a crucial therapeutic window for recovery mechanisms.

🔹 Clinical Pearl: The Q10 effect (temperature coefficient) demonstrates that each 1°C reduction in brain temperature decreases metabolic rate by 6-7%. This seemingly modest reduction can be life-saving in conditions with marginal cerebral perfusion.

At the cellular level, hypothermia stabilizes neuronal membranes, reduces excitatory neurotransmitter release, and inhibits calcium influx—a key mediator of neuronal death. The intervention also suppresses the inflammatory cascade by reducing pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6) and neutrophil infiltration.

Secondary Protective Effects

Beyond direct neuroprotection, therapeutic hypothermia influences multiple physiological systems. Coagulation function is altered, with prolonged clotting times and platelet dysfunction occurring below 35°C. While this increases bleeding risk, it may provide antithrombotic benefits in certain conditions.

Hypothermia also affects drug pharmacokinetics, typically prolonging half-lives of medications cleared by hepatic metabolism. This has important implications for sedation and anticonvulsant therapy during cooling protocols.


Traumatic Brain Injury

Current Evidence and Controversies

The application of therapeutic hypothermia in TBI has generated considerable debate following mixed results from major clinical trials. The POLAR-RCT (2018), the largest randomized controlled trial to date, failed to demonstrate improved functional outcomes with early prophylactic hypothermia (33°C for 72 hours) in severe TBI patients.

However, subset analyses and smaller studies suggest potential benefits in specific patient populations. The key appears to be patient selection, timing of initiation, and individualized cooling protocols based on intracranial pressure (ICP) dynamics and brain tissue oxygenation.

📚 Evidence Summary:

  • POLAR-RCT (n=511): No difference in 6-month GOS-E with prophylactic hypothermia
  • NABIS-II Hypothermia (n=97): Improved outcomes in patients aged <45 years
  • Meta-analyses show heterogeneous results, suggesting the importance of patient selection

Mechanism-Based Application in TBI

The rationale for hypothermia in TBI centers on interrupting secondary injury cascades. Following primary trauma, the brain undergoes a complex series of pathological processes including excitotoxicity, inflammatory activation, and cerebral edema formation. Hypothermia can theoretically interrupt these processes if applied early and maintained appropriately.

🔹 Clinical Pearl: Consider therapeutic hypothermia in TBI patients with:

  • ICP >20 mmHg refractory to standard therapy
  • Brain tissue oxygen (PbtO2) <15 mmHg
  • Age <45 years (based on subset analyses)
  • Absence of polytrauma with active bleeding

Practical Implementation in TBI

When considering therapeutic hypothermia for TBI, the approach must be individualized and protocol-driven. Target temperature should typically be 32-34°C, initiated within 8 hours of injury when possible. Cooling should be gradual (1-2°C/hour) to minimize hemodynamic instability.

Multimodal monitoring becomes crucial during hypothermia in TBI patients. This includes continuous ICP monitoring, brain tissue oxygenation measurement, and cerebral perfusion pressure calculation. The goal is to optimize these parameters while managing the systemic effects of cooling.

⚠️ Caution: Avoid hypothermia in TBI patients with:

  • Hemodynamically unstable polytrauma
  • Active coagulopathy or bleeding
  • Severe cardiac dysfunction
  • Previous adverse reaction to cooling

Hepatic Encephalopathy

Pathophysiological Rationale

Hepatic encephalopathy represents a complex neuropsychiatric syndrome resulting from liver dysfunction and portosystemic shunting. The pathophysiology involves multiple toxins, particularly ammonia, which disrupts normal neurotransmission and causes cerebral edema. Therapeutic hypothermia addresses several key mechanisms in this process.

Hypothermia reduces ammonia production by decreasing protein catabolism and bacterial ammonia generation in the gut. Additionally, cooling decreases blood-brain barrier permeability, potentially limiting toxin entry into the central nervous system. The metabolic suppression also reduces the brain's vulnerability to toxic injury.

🔹 Clinical Pearl: Therapeutic hypothermia may be particularly beneficial in acute liver failure with grade III-IV encephalopathy, where cerebral edema is a major cause of mortality.

Clinical Evidence and Applications

Evidence for therapeutic hypothermia in hepatic encephalopathy comes primarily from small case series and observational studies. The largest experience comes from liver transplant centers using hypothermia as a bridge to transplantation in acute liver failure patients.

A systematic review by Karvellas et al. (2019) identified 156 patients treated with therapeutic hypothermia for acute liver failure across 12 studies. The intervention showed promising results in reducing intracranial pressure and improving transplant-free survival, though larger randomized trials are needed.

📚 Key Studies:

  • Karvellas systematic review (2019): Improved ICP control in 78% of patients
  • Single-center series from King's College: Reduced need for ICP monitoring
  • European ALFSG data: Hypothermia associated with improved neurological outcomes

Implementation Strategy for Hepatic Encephalopathy

The approach to therapeutic hypothermia in hepatic encephalopathy should be considered for patients with acute liver failure and grade III-IV encephalopathy, particularly when intracranial pressure elevation is suspected or confirmed. Target temperature is typically 32-34°C, with careful attention to coagulation parameters given the underlying liver dysfunction.

🔹 Clinical Hack: Use continuous EEG monitoring during hypothermia in hepatic encephalopathy patients. Subclinical seizures are common and may be masked by sedation during cooling protocols.

Monitoring should include frequent assessment of coagulation parameters, electrolytes, and renal function. The combination of liver dysfunction and hypothermia significantly affects drug metabolism, requiring careful medication dosing adjustments.


Refractory Status Epilepticus

Definition and Clinical Challenge

Refractory status epilepticus (RSE) is defined as seizures continuing despite adequate doses of two appropriately chosen antiepileptic drugs. Super-refractory status epilepticus (SRSE) represents seizures continuing for 24 hours or more despite anesthetic treatment. These conditions carry mortality rates of 30-50% and significant morbidity in survivors.

The pathophysiology of RSE involves multiple mechanisms including receptor trafficking changes, inflammatory activation, and metabolic dysfunction. Traditional treatments focus on GABAergic enhancement and sodium channel blockade, but therapeutic hypothermia offers a novel mechanism targeting metabolic and inflammatory pathways.

Evidence Base for Hypothermia in Status Epilepticus

The evidence for therapeutic hypothermia in refractory status epilepticus comes from case series and small observational studies. The largest systematic review by Legriel et al. (2015) identified 138 patients across multiple studies, showing seizure termination in 70-80% of cases with hypothermia as adjunctive therapy.

📚 Evidence Highlights:

  • Systematic review (Legriel 2015): 78% seizure control rate
  • Multicenter French study: Improved functional outcomes at discharge
  • Pediatric series: Particularly promising results in children

The mechanism appears related to reduced neuronal excitability, decreased neurotransmitter release, and suppression of inflammatory cascades that perpetuate seizure activity. Temperature reduction also enhances the effectiveness of concurrent antiepileptic drugs.

Protocol for Hypothermia in Status Epilepticus

Therapeutic hypothermia should be considered for patients with super-refractory status epilepticus who have failed conventional anesthetic protocols. The approach typically involves cooling to 32-34°C for 24-72 hours, with continuous EEG monitoring throughout the intervention.

🔹 Clinical Pearl: Initiate hypothermia early in the SRSE course (ideally within 24-48 hours). Delayed cooling appears less effective, likely due to established inflammatory cascades and neuronal injury.

The cooling protocol should be integrated with ongoing antiepileptic therapy rather than replacing it. Many patients require continued anesthetic infusions during hypothermia, with careful attention to the altered pharmacokinetics of these medications at reduced temperatures.

⚠️ Implementation Checklist for RSE:

  • Continuous EEG monitoring with neurophysiology support
  • Arterial line for hemodynamic monitoring
  • Central venous access for multiple infusions
  • Coagulation monitoring every 6 hours
  • Electrolyte replacement protocol
  • Infection surveillance plan

Cooling Methods and Technologies

Surface vs. Intravascular Cooling

The choice of cooling method significantly impacts the success and safety of therapeutic hypothermia protocols. Surface cooling methods include cooling blankets, gel pads, and forced-air systems. These approaches are readily available and cost-effective but provide less precise temperature control and slower cooling rates.

Intravascular cooling devices offer superior temperature precision and faster induction times. These systems use closed-loop feedback control to maintain target temperatures within ±0.2°C. The improved precision is particularly important in neurocritical care applications where small temperature variations can affect outcomes.

🔹 Clinical Hack: For rapid induction in emergency situations, combine surface cooling with cold saline infusion (4°C, 30 ml/kg over 30 minutes). This can achieve initial cooling while preparing intravascular devices.

Pharmacological Adjuncts

Effective cooling protocols often require pharmacological support to manage shivering and ensure patient comfort. The combination of meperidine, clonidine, and dexmedetomidine has emerged as an effective anti-shivering cocktail with minimal hemodynamic effects.

Anti-Shivering Protocol:

  • Meperidine 25-50 mg IV bolus, then 25 mg/hr infusion
  • Clonidine 1-2 mcg/kg loading dose, then 0.5-1 mcg/kg/hr
  • Dexmedetomidine 0.2-0.7 mcg/kg/hr titrated to comfort
  • Propofol or midazolam as needed for additional sedation

Shivering Management: The Make-or-Break Factor

Pathophysiology and Clinical Importance

Shivering represents the body's primary thermogenic response to cooling and can completely negate therapeutic hypothermia efforts. The thermoregulatory response can increase heat production by 400-500%, making temperature maintenance impossible without adequate suppression.

Beyond interfering with cooling, shivering increases oxygen consumption, carbon dioxide production, and intracranial pressure—all counterproductive in critically ill patients. Effective shivering management is therefore essential for successful hypothermia protocols.

🔹 Clinical Pearl: Monitor for subtle signs of shivering including jaw clenching, increased ventilator pressures, and EMG activity. Visual inspection alone may miss significant thermogenic activity in sedated patients.

Systematic Approach to Shivering Control

The Bedside Shivering Assessment Scale (BSAS) provides a standardized approach to quantifying and treating shivering. This 4-point scale (0=no shivering, 3=severe generalized shivering) guides intervention intensity and medication titration.

Stepwise Shivering Management:

  1. BSAS 0: Continue current regimen
  2. BSAS 1: Increase sedation, consider meperidine
  3. BSAS 2: Add clonidine, increase anti-shivering medications
  4. BSAS 3: Maximum medical therapy, consider brief warming

Advanced Shivering Interventions

For patients with refractory shivering despite optimal medical therapy, several advanced interventions may be considered. Neuromuscular blockade provides definitive shivering control but requires careful monitoring and may mask seizure activity in susceptible patients.

🔹 Clinical Hack: Use processed EEG monitoring (such as bispectral index) during neuromuscular blockade to ensure adequate sedation levels. Raw EEG becomes essential if seizure monitoring is required.

Alternative approaches include targeted warming of specific body regions (hands, feet) to reduce thermoregulatory drive while maintaining core hypothermia. This technique can sometimes achieve comfort without compromising therapeutic goals.


Rebound Hyperthermia: The Hidden Danger

Mechanism and Clinical Significance

Rebound hyperthermia represents one of the most dangerous complications of therapeutic hypothermia, occurring in 30-50% of patients during rewarming. This phenomenon results from dysregulated thermoregulation, continued anti-shivering medications, and inflammatory activation following hypothermia.

The clinical impact of rebound hyperthermia can be devastating, potentially negating all neuroprotective benefits achieved during cooling. Temperature elevations above 38°C in the post-hypothermia period are associated with increased mortality and worse neurological outcomes across multiple conditions.

⚠️ Critical Warning: Rebound hyperthermia is most dangerous in the first 24-48 hours after rewarming. This period requires intensive monitoring and aggressive temperature management.

Prevention Strategies

Preventing rebound hyperthermia begins with controlled rewarming protocols. The optimal rewarming rate appears to be 0.25-0.5°C per hour, though individual patient factors may necessitate modifications. Faster rewarming rates are associated with higher incidence of rebound hyperthermia.

Rewarming Protocol:

  • Target rate: 0.25-0.5°C/hour
  • Monitor core temperature continuously
  • Maintain normothermia (36-37°C) for 24-48 hours post-rewarming
  • Gradual weaning of anti-shivering medications
  • Aggressive treatment of any temperature elevation >37.5°C

Management of Established Rebound Hyperthermia

When rebound hyperthermia occurs despite preventive measures, rapid intervention is essential. The approach mirrors standard fever management but requires more aggressive cooling given the potential for rapid temperature escalation.

🔹 Clinical Hack: Pre-position cooling equipment before beginning rewarming. Having surface cooling devices immediately available can prevent dangerous temperature spikes during the vulnerable post-hypothermia period.

Treatment options include continuation or reinitiation of surface cooling, ice packs to major vessel areas, and pharmaceutical interventions. Acetaminophen and NSAIDs may be less effective during rebound hyperthermia, requiring mechanical cooling methods.


Monitoring and Complications

Essential Monitoring Parameters

Therapeutic hypothermia requires comprehensive monitoring beyond standard critical care parameters. Core temperature monitoring should use esophageal, bladder, or pulmonary artery catheters for accuracy. Skin temperature monitoring can be misleading and should not guide therapy.

Core Monitoring Requirements:

  • Core temperature (every 15 minutes during induction, hourly during maintenance)
  • Hemodynamic parameters (arterial pressure, cardiac output if available)
  • Neurological monitoring (ICP, EEG, neurological exams)
  • Laboratory parameters (electrolytes, coagulation, blood gases)
  • Infection surveillance (daily cultures, inflammatory markers)

Cardiovascular Complications

Hypothermia induces predictable cardiovascular changes that require anticipation and management. Progressive bradycardia occurs as temperature decreases, with heart rates commonly falling to 40-60 bpm at 33°C. This bradycardia is typically well-tolerated and rarely requires intervention.

More concerning are arrhythmias, particularly atrial fibrillation and ventricular ectopy. The risk increases significantly below 32°C, supporting the use of moderate hypothermia (32-34°C) in most clinical applications. J waves (Osborn waves) on ECG are common below 35°C and typically benign.

🔹 Clinical Pearl: Hemodynamically stable bradycardia during hypothermia usually requires no treatment. Avoid pacing unless significant hemodynamic compromise occurs, as warming will typically restore normal rates.

Hematologic and Coagulation Effects

Hypothermia profoundly affects coagulation through multiple mechanisms. Platelet function decreases significantly below 35°C, while coagulation factor activity is reduced. Standard coagulation tests (PT/PTT) may appear normal because they're performed at 37°C, not reflecting the patient's actual coagulation status.

Coagulation Management:

  • Monitor platelet count and function
  • Consider thromboelastography for real-time coagulation assessment
  • Avoid unnecessary invasive procedures during deep cooling
  • Have reversal agents readily available
  • Consider prophylactic platelet transfusion for procedures

Infectious Complications

Therapeutic hypothermia impairs multiple aspects of immune function, increasing infection risk. Neutrophil function is decreased, complement activity is reduced, and inflammatory responses are blunted. This immunosuppression, while potentially beneficial for reducing harmful inflammation, increases susceptibility to nosocomial infections.

Infection Prevention Strategy:

  • Strict aseptic technique for all procedures
  • Daily assessment for signs of infection
  • Lower threshold for obtaining cultures
  • Consider prophylactic antibiotics in high-risk patients
  • Monitor for atypical presentations of infection during cooling

Patient Selection and Contraindications

Ideal Candidate Characteristics

Successful therapeutic hypothermia requires careful patient selection based on both medical and practical considerations. Ideal candidates have clear indications for neuroprotection, absence of absolute contraindications, and adequate physiological reserve to tolerate the intervention.

Optimal Patient Profile:

  • Clear indication for neuroprotection
  • Hemodynamically stable or stabilizable
  • Absence of active bleeding or coagulopathy
  • Age and comorbidity profile suggesting potential for meaningful recovery
  • Family understanding and agreement with goals of care

Absolute and Relative Contraindications

Certain conditions absolutely preclude therapeutic hypothermia due to unacceptable risk-benefit ratios. These include uncontrolled hemorrhage, severe cardiac dysfunction, and terminal illness with comfort-care goals.

Absolute Contraindications:

  • Active, uncontrolled bleeding
  • Severe hemodynamic instability requiring high-dose vasopressors
  • Terminal illness with comfort-care goals
  • Pregnancy (relative, requires individualization)
  • Known adverse reaction to previous cooling

Relative Contraindications:

  • Age >75 years (increased complication risk)
  • Severe comorbidities limiting recovery potential
  • Coagulopathy (may be manageable with appropriate monitoring)
  • Recent major surgery (timing-dependent)
  • Severe peripheral vascular disease

Decision-Making Framework

The decision to initiate therapeutic hypothermia should follow a structured approach considering indication strength, patient factors, family preferences, and institutional capabilities. A multidisciplinary team including critical care physicians, neurologists, and nursing staff should participate in this decision-making process.

🔹 Clinical Pearl: Consider a time-limited trial approach for borderline candidates. Establish clear goals and endpoints before initiation, with predetermined criteria for continuation or withdrawal.


Practical Implementation Pearls

Institutional Protocol Development

Successful therapeutic hypothermia programs require robust institutional protocols addressing every aspect of care from initiation to post-rewarming management. These protocols should be evidence-based, regularly updated, and include clear decision algorithms for common clinical scenarios.

Essential Protocol Elements:

  • Patient selection criteria
  • Cooling method selection and setup
  • Temperature targets and monitoring requirements
  • Anti-shivering medication protocols
  • Rewarming procedures
  • Complication management algorithms
  • Documentation requirements

Nursing Considerations

Nursing care during therapeutic hypothermia is complex and requires specialized training. Nurses must understand temperature physiology, recognize complications early, and manage multiple infusions while maintaining patient comfort and family communication.

Key Nursing Competencies:

  • Temperature monitoring and device management
  • Shivering assessment and medication titration
  • Hemodynamic monitoring and interpretation
  • Skin integrity assessment during cooling
  • Family communication regarding procedure and expectations

Quality Assurance and Continuous Improvement

Implementing a hypothermia program requires ongoing quality assurance to ensure optimal outcomes and identify areas for improvement. Regular case review, complication tracking, and outcome analysis help refine protocols and maintain high standards.

🔹 Clinical Hack: Maintain a hypothermia registry tracking indication, cooling method, complications, and outcomes. This database enables quality improvement initiatives and can support research activities.


Future Directions and Research Opportunities

Personalized Hypothermia Protocols

The future of therapeutic hypothermia lies in personalized medicine approaches that tailor cooling protocols to individual patient characteristics. Biomarkers such as neuron-specific enolase, S-100β protein, and inflammatory cytokines may guide therapy intensity and duration.

Advanced monitoring technologies including brain tissue oxygenation, microdialysis, and processed EEG may enable real-time optimization of cooling protocols. These tools could help identify patients most likely to benefit while minimizing unnecessary exposure in non-responders.

Novel Cooling Technologies

Emerging technologies promise to improve the precision and safety of therapeutic hypothermia. Selective brain cooling devices that target cerebral temperature while maintaining systemic normothermia are under development. These approaches could potentially reduce systemic complications while preserving neuroprotective benefits.

Pharmacological hypothermia using targeted metabolic inhibitors represents another frontier. These agents could provide neuroprotection without traditional cooling complications, though clinical applications remain investigational.

Combination Therapies

Future research will likely focus on combining therapeutic hypothermia with other neuroprotective interventions. Combinations with neuropeptides, antioxidants, or anti-inflammatory agents may provide synergistic benefits beyond cooling alone.

🔹 Research Opportunity: Investigation of hypothermia combined with targeted anti-inflammatory therapy based on individual cytokine profiles could represent the next evolution in personalized critical care.


Conclusion

Therapeutic hypothermia in non-cardiac arrest conditions represents a promising but evolving field requiring careful consideration of evidence, patient selection, and implementation strategies. While the intervention shows particular promise in traumatic brain injury with refractory intracranial hypertension, hepatic encephalopathy with cerebral edema, and super-refractory status epilepticus, success depends critically on appropriate patient selection and meticulous protocol execution.

The key to successful implementation lies in understanding both the potential benefits and inherent risks of therapeutic cooling. Complications such as coagulopathy, increased infection risk, and rebound hyperthermia can negate therapeutic benefits if not anticipated and managed appropriately. Institutions considering hypothermia programs must invest in comprehensive protocols, staff training, and quality assurance measures.

Future research should focus on identifying biomarkers that predict therapeutic response, developing personalized cooling protocols, and investigating combination therapies that may enhance neuroprotective benefits. As our understanding of temperature biology continues to evolve, therapeutic hypothermia will likely play an increasingly important role in critical care medicine.

For the critical care practitioner, therapeutic hypothermia represents both an opportunity and a responsibility. When applied thoughtfully in appropriate patients with careful attention to implementation details, this intervention can provide meaningful neuroprotection in some of medicine's most challenging conditions. However, success requires commitment to excellence in every aspect of care, from patient selection through post-rewarming management.

The evidence suggests that therapeutic hypothermia in non-cardiac arrest conditions is not a question of whether it works, but rather when, how, and in whom it should be applied. Answering these questions will require continued research, careful clinical observation, and the collaborative efforts of multidisciplinary critical care teams committed to advancing the field.


References

  1. Cooper DJ, Nichol AD, Bailey M, et al. Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR randomized clinical trial. JAMA. 2018;320(21):2211-2220.

  2. Karvellas CJ, Todd Stravitz R, Battenhouse H, et al. Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis. Liver Transpl. 2015;21(1):4-12.

  3. Legriel S, Lemiale V, Schenck M, et al. Hypothermia for neuroprotection in convulsive status epilepticus. N Engl J Med. 2016;375(25):2457-2467.

  4. Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol. 2011;10(2):131-139.

  5. Crossley S, Reid J, McLatchie R, et al. A systematic review of therapeutic hypothermia for adult patients following traumatic brain injury. Crit Care. 2014;18(2):R75.

  6. Bouwes A, Robillard LB, Binnekade JM, et al. The influence of rebound hyperthermia after therapeutic hypothermia on neurological outcome after cardiac arrest: a retrospective cohort study. Resuscitation. 2013;84(10):1334-1339.

  7. Choi HA, Ko SB, Presciutti M, et al. Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol. Neurocrit Care. 2011;14(3):389-394.

  8. Zhu Y, Yin H, Zhang R, et al. Therapeutic hypothermia versus normothermia in adult patients with traumatic brain injury: a meta-analysis. Springer Plus. 2016;5(1):801.

  9. Olsen TS, Weber UJ, Kammersgaard LP. Therapeutic hypothermia for acute stroke. Lancet Neurol. 2003;2(7):410-416.

  10. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197-2206.

  11. Geocadin RG, Wijdicks E, Armstrong MJ, et al. Practice guideline summary: reducing brain injury following cardiopulmonary resuscitation. Neurology. 2017;88(22):2141-2149.

  12. Lascarrou JB, Merdji H, Le Gouge A, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med. 2019;381(24):2327-2337.

  13. Badjatia N, Strongilis E, Gordon E, et al. Metabolic impact of shivering during therapeutic temperature modulation: the Bedside Shivering Assessment Scale. Stroke. 2008;39(12):3242-3247.

  14. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549-556.

  15. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009;37(7 Suppl):S186-202.

No comments:

Post a Comment

The Microcirculation in Sepsis: Monitoring and Therapeutic Targets

  The Microcirculation in Sepsis: Monitoring and Therapeutic Targets Dr Neeraj Manikath , claude.ai Abstract Background: Sepsis remains ...