Procedural Sedation and Analgesia: Safer and Smarter

Dr Neeraj Manikath , claude.ai

Abstract

Procedural sedation and analgesia (PSA) has evolved from an art practiced by intuition to a science underpinned by pharmacological precision and safety protocols. This review examines contemporary best practices in PSA, with particular emphasis on ketamine as the workhorse agent, systematic management of adverse events including laryngospasm and emergence phenomena, and nuanced approaches to special populations. Drawing on current evidence and decades of clinical experience, we present practical pearls that transform good sedation practice into exceptional patient care.

Introduction

Procedural sedation and analgesia represents one of the most frequently performed interventions in acute care settings, yet it remains fraught with potential complications when performed without systematic rigor. The modern intensivist must balance the competing demands of patient comfort, procedural success, hemodynamic stability, and airway safety—all while maintaining vigilance for rare but catastrophic complications.

The evolution of PSA has been marked by three paradigm shifts: first, the recognition that fasting guidelines from the operating room need not apply uniformly to emergency settings; second, the acceptance of dissociative sedation as distinct from traditional sedation-analgesia continua; and third, the understanding that adverse events are often preventable through anticipation rather than merely manageable through reaction.

Ketamine: The Workhorse Drug for PSA

Pharmacological Profile

Ketamine, a phencyclidine derivative, induces a unique state termed "dissociative sedation" characterized by functional and electrophysiological dissociation between the thalamus and limbic system. Unlike traditional sedative-hypnotics that depress the central nervous system along a continuum, ketamine produces catalepsy, amnesia, and profound analgesia while preserving protective airway reflexes and cardiorespiratory stability.

The pharmacokinetics of ketamine are particularly favorable for PSA. Following intravenous administration, onset occurs within 30-60 seconds, with peak effect at 1-2 minutes and duration of 10-20 minutes. Redistribution from the CNS to peripheral tissues explains its relatively brief duration of action despite a longer elimination half-life of 2-3 hours. Intramuscular administration, while slower (onset 3-5 minutes, peak 5-10 minutes), provides reliable absorption when intravenous access is challenging—a particularly valuable attribute in the uncooperative pediatric or agitated patient.

Clinical Advantages: Why Ketamine Dominates PSA

Cardiovascular Stability: Unlike propofol or benzodiazepines, ketamine stimulates the sympathetic nervous system, resulting in maintained or increased blood pressure and heart rate. This sympathomimetic effect proves invaluable in the hemodynamically unstable patient, though caution is warranted in patients with coronary disease where increased myocardial oxygen demand may precipitate ischemia.

Respiratory Preservation: Perhaps ketamine's most celebrated attribute is preservation of respiratory drive and protective airway reflexes. While not absolute—respiratory depression can occur, particularly with rapid bolus administration or co-administration of other sedatives—the incidence is substantially lower than with traditional agents. This characteristic makes ketamine particularly attractive for PSA in locations where immediate airway rescue may be challenging.

Profound Analgesia: Ketamine's NMDA receptor antagonism provides potent analgesia that persists beyond the dissociative effects. Sub-dissociative doses (0.1-0.3 mg/kg IV) can serve as effective adjuncts to opioid analgesia, potentially reducing opioid requirements and associated side effects.

Dosing Strategies: The Devil in the Details

Standard IV Dosing: For adults, 1-2 mg/kg IV administered over 30-60 seconds typically achieves adequate dissociation. The critical error lies in inadequate initial dosing, leading to an inadequate plane of sedation, patient distress, and the need for supplemental doses that prolong recovery. Underdosing is more problematic than modest overdosing.

Intramuscular Route: When IV access is unavailable or impractical, 4-5 mg/kg IM provides reliable dissociation. The IM route is particularly valuable in the combative patient requiring emergent procedures or in pediatric populations where IV placement may prove the most traumatic aspect of care.

Pediatric Considerations: Children typically require the higher end of dosing ranges (1.5-2 mg/kg IV, 4-5 mg/kg IM) due to increased volume of distribution and faster clearance. The mistake of adult-dose extrapolation frequently results in inadequate sedation.

Supplemental Dosing: If initial dosing proves insufficient, supplemental doses of 0.5 mg/kg IV (one-quarter to one-half the initial dose) may be administered. However, supplemental dosing increases the risk of prolonged recovery and emergence reactions.

Pearl: The "Ketamine Drift"

Experienced practitioners recognize the phenomenon of "ketamine drift"—the patient who appears adequately dissociated initially but gradually becomes more responsive during prolonged procedures. Rather than immediately administering supplemental ketamine, consider whether the procedure can be completed expeditiously. If supplementation is necessary, smaller incremental doses (0.25-0.5 mg/kg) are preferable to repeated full induction doses.

Oyster: Ketamine is NOT Absolutely Airway-Protective

The most dangerous misconception about ketamine is that it absolutely preserves airway reflexes. While protective reflexes are generally maintained, laryngospasm, excessive salivation leading to airway obstruction, and apnea can occur. Every ketamine sedation must be approached with the same airway preparedness as any other deep sedation. The availability of bag-valve-mask ventilation, suction, and airway rescue equipment is non-negotiable.

Contraindications: Real and Theoretical

Absolute Contraindications (rare):

Known hypersensitivity to ketamine
Conditions where elevated intracranial pressure would be dangerous (though this remains controversial in modern literature)
Age less than 3 months (limited safety data)

Relative Contraindications (require risk-benefit assessment):

Uncontrolled hypertension or cardiovascular instability where sympathetic stimulation is undesirable
Acute globe injury (though evidence for increased intraocular pressure is conflicting)
Psychosis or severe psychiatric disturbance
Thyroid dysfunction (particularly hyperthyroidism)

The historical contraindication of head injury has been largely abandoned, as emerging evidence suggests ketamine may not increase intracranial pressure in ventilated patients and may even have neuroprotective properties.

Managing Adverse Events: Laryngospasm and Emergence Reactions

Laryngospasm: Recognition and Management

Laryngospasm represents the most serious respiratory complication of ketamine sedation, occurring in approximately 0.4-1.4% of pediatric cases and less frequently in adults. It manifests as complete or partial closure of the vocal cords, resulting in high-pitched inspiratory stridor or complete airway obstruction.

Risk Factors:

Age less than 5 years or greater than 13 years (bimodal distribution in pediatric population)
Upper respiratory infection within 2 weeks (relative risk increases 2-5 fold)
Reactive airway disease
Stimulation of the oropharynx during inadequate depth of sedation
Excessive salivation with pooling of secretions

Prevention Strategies:

Antisialagogue administration: Glycopyrrolate (0.005-0.01 mg/kg IV, maximum 0.2 mg) or atropine (0.01 mg/kg IV) administered 3-5 minutes before ketamine reduces salivation. While not universally practiced, antisialagogues are particularly valuable in young children, prolonged procedures, or when airway manipulation is anticipated.
Depth of sedation: Laryngospasm most commonly occurs during light planes of dissociation. Ensuring adequate initial dosing and avoiding premature stimulation are critical.
Gentle suctioning: When suctioning is necessary, use gentle technique and avoid posterior pharyngeal stimulation.

Management Algorithm:

Immediate recognition: High index of suspicion with any change in respiratory pattern
Positive pressure ventilation: Gentle bag-valve-mask with 100% oxygen, maintaining a tight seal
CPAP: Continuous positive airway pressure (10-15 cm H₂O) often breaks the spasm
Larson's maneuver: Firm pressure applied bilaterally at the "laryngospasm notch" (behind the lobule of the ear, between the mandible and mastoid process) combined with anterior jaw thrust
Pharmacological intervention: If not rapidly responsive, consider:
- Propofol 0.5-1 mg/kg IV (deepens sedation, relaxes laryngeal musculature)
- Succinylcholine 0.1-0.5 mg/kg IV (in extremis, requires advanced airway management capability)

Hack: The "Ketamine Cough"

Brief coughing immediately following ketamine administration, sometimes accompanied by transient oxygen desaturation, represents excessive salivation with microaspiration rather than true laryngospasm. This typically resolves spontaneously and does not require intervention beyond repositioning and gentle suctioning. Distinguishing this benign phenomenon from true laryngospasm prevents unnecessary escalation of intervention.

Emergence Reactions: Prevention and Management

Emergence reactions occur in 5-30% of adult patients, manifesting as agitation, dysphoria, vivid dreams, hallucinations, or delirium during recovery. Pediatric patients experience substantially lower rates (1-5%), likely due to developmental differences in dream interpretation and anxiety.

Risk Factors:

Age greater than 16 years
Female sex
Baseline anxiety or psychiatric history
Doses exceeding 2 mg/kg
History of frequent dreaming or nightmares
Stimulating recovery environment

Prevention Strategies:

Benzodiazepine co-administration: Midazolam 0.03-0.05 mg/kg IV (typically 1-2 mg in adults) administered either 3-5 minutes before ketamine or concurrently reduces emergence phenomena by 50-70%. The trade-off is prolonged recovery time and potential synergistic respiratory depression.
Environmental modification: Minimize auditory and visual stimulation during recovery. Dim lights, reduce noise, and limit unnecessary physical examination or conversation.
Patient selection and preparation: Frank discussion of potential dream-like experiences may reduce anxiety when they occur. Avoid ketamine in patients with severe anxiety about dissociative experiences.

Management of Established Reactions:

Reassurance: Verbal orientation that the experience is temporary and expected
Benzodiazepines: Midazolam 1-2 mg IV for severe agitation
Time: Most reactions resolve within 15-30 minutes without intervention
Physical restraint: Avoid unless necessary for patient safety, as it may intensify dysphoria

Pearl: Recovery Room Coaching

Instruct recovery room staff that patients emerging from ketamine sedation should be allowed to "wake up at their own pace" without aggressive stimulation. Premature attempts to orient or examine patients frequently trigger or intensify emergence reactions. A quiet, dimly lit space with minimal interaction until the patient spontaneously engages proves optimal.

Special Populations: Pediatric, Elderly, and High-Risk Patients

Pediatric PSA: Unique Considerations

The pediatric population represents both the ideal and the most challenging scenario for PSA. Children benefit dramatically from sedation that transforms potentially traumatic procedures into tolerable experiences, yet their smaller physiological reserves make adverse events potentially more consequential.

Developmental Differences:

Infants (<6 months): Higher risk of apnea, less predictable drug response, limited ability to cooperate with monitoring
Toddlers (1-3 years): Maximal anxiety with separation, potential for airway obstruction from large tongue and tonsillar tissue
School-age (4-10 years): Generally optimal candidates for PSA, able to cooperate with monitoring
Adolescents: Increased risk of emergence reactions, approaching adult dosing requirements

Fasting Considerations in Pediatrics: Traditional NPO guidelines (nothing by mouth for 6-8 hours) have been liberalized for emergency PSA. Current evidence suggests that the aspiration risk in emergency procedures is not meaningfully increased by recent food intake, while strict fasting may increase anxiety, dehydration, and hypoglycemia. Most emergency medicine and pediatric emergency medicine societies now accept that urgent procedures should not be delayed for fasting, though elective procedures may justify waiting when clinically reasonable.

Dosing Pearls:

Weight-based calculations should use actual body weight, not ideal body weight
Consider IM route early in the uncooperative child rather than traumatizing with prolonged IV attempts
Intranasal ketamine (3-5 mg/kg) offers an alternative non-invasive route, though bioavailability is variable

Pediatric Hack: The "Pre-oxygenation Protocol"

In young children, establish baseline oxygen saturation and apply oxygen by blow-by or nasal cannula 2-3 minutes before ketamine administration. This pre-oxygenation provides an oxygen reservoir that extends the time to desaturation if apnea or laryngospasm occurs, buying critical seconds for intervention. Avoid frightening the child with a tight-fitting mask; passive oxygen delivery is sufficient.

Geriatric PSA: Respecting Reduced Reserve

The elderly patient presents challenges of polypharmacy, comorbid disease, and reduced physiological reserve. Age-related pharmacokinetic and pharmacodynamic changes mandate dosing adjustments and heightened vigilance.

Physiological Considerations:

Decreased cardiac output prolongs circulation time, delaying drug effect
Reduced lean body mass and total body water increase drug concentration
Decreased hepatic metabolism and renal clearance prolong drug effect
Impaired baroreceptor reflexes increase risk of hypotension
Baseline cognitive impairment may be difficult to distinguish from sedation effects

Dosing Modifications: Reduce ketamine dosing by 30-50% in patients over 65 years, using 0.5-1 mg/kg IV for initial dosing. The adage "start low and go slow" applies universally to geriatric sedation. Titration to effect with smaller incremental doses (0.25 mg/kg) reduces the risk of oversedation.

Comorbidity Considerations:

Cardiac disease: While ketamine's sympathomimetic effects generally support blood pressure, coronary disease patients may not tolerate increased myocardial oxygen demand. Consider alternative agents or very cautious dosing with nitrate availability.
Cognitive impairment: Baseline dementia increases risk of delirium. Document baseline mental status carefully.
Polypharmacy: Drug interactions, particularly with benzodiazepines, opioids, or antihypertensives, may be synergistic.

Pearl: The Geriatric Recovery Challenge

Elderly patients frequently require prolonged recovery periods despite receiving reduced dosing. Plan for extended post-procedure monitoring (60-90 minutes rather than the typical 30-45 minutes) and have low threshold for observation admission if recovery is incomplete. The pressure to expedite throughput should never compromise safe discharge.

High-Risk Patients: Obesity, OSA, and Critical Illness

Obese Patients: Obesity presents unique challenges for PSA, including difficult IV access, challenging bag-valve-mask ventilation if needed, higher aspiration risk, and baseline hypoxemia. Ketamine dosing should be based on total body weight rather than ideal body weight, as ketamine is lipophilic with a high volume of distribution. Position the obese patient in reverse Trendelenburg (head elevated 20-30 degrees) to optimize functional residual capacity and reduce aspiration risk.

Obstructive Sleep Apnea (OSA): Patients with diagnosed or suspected OSA (witnessed apnea, loud snoring, obesity, daytime somnolence) are at increased risk of airway obstruction during sedation. While ketamine's airway-preserving properties make it preferable to other agents, increased vigilance is mandatory. Consider:

Pre-procedure continuous positive airway pressure (CPAP) for known OSA patients
Aggressive jaw thrust and airway positioning during sedation
Extended monitoring during recovery
Lower threshold for consultation with anesthesia for alternative approaches

Critically Ill Patients: PSA in the critically ill intensive care patient requires modification of standard approaches:

Hemodynamic instability: While ketamine supports blood pressure in most patients, the catecholamine-depleted patient in distributive shock may paradoxically experience hypotension due to ketamine's intrinsic myocardial depressant effects unmasked when sympathetic compensation is exhausted. Consider push-dose pressors availability.
Elevated intracranial pressure: Modern evidence suggests ketamine may be acceptable, but consultation with neurosurgery and careful blood pressure management are prudent.
Respiratory failure: Pre-procedure optimization of oxygenation and ventilation, consideration of non-invasive positive pressure ventilation during PSA, and immediate availability of advanced airway equipment are essential.

Hack: The "Ketamine Bridge"

In the critically ill patient requiring semi-urgent procedures (chest tube placement, cardioversion, orthopedic reduction), ketamine serves as an excellent "bridge" sedative when transitioning from ICU sedation. Rather than allowing propofol or dexmedetomidine infusions to wear off completely before the procedure, administer ketamine while baseline sedation is still present but lightened. This approach maintains comfort while exploiting ketamine's unique cardiovascular profile. Careful titration is essential to avoid excessive sedation depth.

Monitoring and Safety Systems

Regardless of agent or population, systematic monitoring forms the foundation of safe PSA. Standard monitoring includes:

Continuous pulse oximetry
Continuous capnography (particularly valuable for early detection of hypoventilation before oxygen desaturation)
Intermittent blood pressure monitoring (every 3-5 minutes during procedure, every 5-10 minutes during recovery)
Continuous electrocardiography in patients with cardiac disease
Continuous visual observation by a dedicated provider

The concept of "procedural pause" borrowed from the operating room applies equally to PSA. Before administering sedation, verify: patient identity, procedure planned, informed consent obtained, fasting status documented, pre-procedure assessment completed, monitoring equipment functional, airway equipment immediately available, and recovery area prepared.

Conclusion

Procedural sedation and analgesia represents a high-stakes intervention where excellence depends upon systematic preparation, pharmacological precision, and anticipation of complications. Ketamine's unique pharmacological profile establishes it as the workhorse agent for PSA, but its use demands respect for potential adverse events and modification for special populations.

The competent intensivist approaches each PSA as a miniature anesthetic, with the same rigor and preparation afforded to operating room cases. The excellent intensivist recognizes that superior outcomes emerge not from managing complications expertly but from preventing them systematically through attention to detail, appropriate patient selection, optimal dosing, and vigilant monitoring.

As we advance PSA practice, the goal extends beyond procedural success to encompass patient experience, safety culture, and outcome optimization. In this framework, ketamine emerges not merely as a drug but as an enabler of compassionate, effective acute care.

Key Pearls Summary

Dosing confidence: Underdosing ketamine creates more problems than modest overdosing
Antisialagogues: Consider routinely in children and prolonged procedures
Environmental control: Recovery environment profoundly influences emergence reactions
Age-adjusted approach: Reduce dosing 30-50% in elderly, increase dosing in children
Capnography: Detects respiratory compromise earlier than pulse oximetry alone
Preparation: Equipment for airway rescue must be immediately available, not "nearby"
Recovery patience: Avoid premature stimulation during emergence
Risk stratification: OSA, obesity, and critical illness demand heightened vigilance

References (Selected Key Literature):

Green SM, Roback MG, Krauss B, et al. Predictors of airway and respiratory adverse events with ketamine sedation in the emergency department. Ann Emerg Med. 2009;54(2):158-168.
Bhatt M, Johnson DW, Chan J, et al. Risk factors for adverse events in emergency department procedural sedation for children. JAMA Pediatr. 2017;171(10):957-964.
Godwin SA, Burton JH, Gerardo CJ, et al. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014;63(2):247-258.
Messenger DW, Murray HE, Dungey PE, et al. Subdissociative-dose ketamine versus fentanyl for analgesia during propofol procedural sedation. Acad Emerg Med. 2008;15(10):877-886.
Roback MG, Carlson DW, Babl FE, et al. Update on pharmacological management of procedural sedation for children. Curr Opin Anaesthesiol. 2016;29(Suppl 1):S21-S35.
Andolfatto G, Abu-Laban RB, Zed PJ, et al. Ketamine-propofol combination (ketofol) versus propofol alone for emergency department procedural sedation and analgesia. Ann Emerg Med. 2012;59(6):504-512.
Scherzer D, Leder M, Tobias JD. Pro-con debate: etomidate or ketamine for rapid sequence intubation in pediatric patients. J Pediatr Pharmacol Ther. 2012;17(2):142-149.
Miner JR, Moore JC, Austad EJ, et al. Randomized, double-blinded, clinical trial of propofol, 1:1 propofol/ketamine, and 4:1 propofol/ketamine for deep procedural sedation in the emergency department. Ann Emerg Med. 2015;65(5):479-488.

Word count: Approximately 3,800 words

Author's Note: This review reflects contemporary evidence-based practice in PSA while acknowledging that protocols continue to evolve. Practitioners should adapt recommendations to their institutional guidelines, patient populations, and clinical expertise.

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Friday, November 7, 2025