Complications of Procedural Sedation

Background: As Emergency Department (ED) physicians it is not uncommon to give patients procedural sedation and analgesia (PSA) to help facilitate painful procedures. Performing PSA requires close monitoring and is not without potential adverse events. There are numerous analgesic, sedative, and anesthetic agents that can be used in combination for PSA in the ED. Adverse event reporting for PSA has been heterogeneous. The purpose of this systematic review and meta-analysis is to determine the incidence of adverse events during PSA in the ED, including the frequency of events with individual drugs and different drug combinations.

What Article are we Reviewing:

Bellolio MF et al. Incidence of Adverse Events in Adults Undergoing Procedural Sedation in the Emergency Department: A Systematic Review and Meta-Analysis. Acad Emerg Med 2016; 23: 119 – 134. PMID: 26801209

What They Did:

• Systematic Review and Meta-Analysis to evaluate the incidence of adverse events in adults undergoing procedural sedation in the ED.
• Included RCTs and Observational studies published after 2005, in which PSA was performed on adults in the ED
• Included randomized controlled trials and observational studies of adults (> 18 years).

Outcomes:

• Estimated incidence per 1,000 patients with 95% CI for agitation, apnea, aspiration, bradycardia, bradypnea, hypotension, hypoxia, intubation, laryngospasm, and nausea/vomiting

Results:

• Search found 2046 titles for review
  • 55 articles, with 9,652 procedural sedations, were eligible for inclusion
  • 25 were RCTs
  • 30 were Observational studies
• Most Frequent Events:
  • Hypoxia: 40.2 per 1,000 sedations
  • Vomiting: 16.4 per 1,000 sedations
  • Hypotension: 15.2 per 1,000 sedations
  • Apnea: 12.4 per 1,000 sedations
• Severe Adverse Events Requiring Emergent Medical Intervention:
  • Aspiration 1.2 per 1,000 sedations
  • Laryngospasm: 4.2 per 1,000 sedations
  • Intubation: 1.6 per 1,000 sedations

Results by Outcome:

• Subgroup Analysis of Hypoxia
  • O2 Sat < 90%: 23.0 per 1,000 sedations
  • O2 Sat <94%: 73.1 per 1,000 sedations
  • O2 Sat <95%: 230.7 per 1,000 sedations
• Sensitivity Analysis
  • Observational studies excluded (Incidence of adverse events in PSA Significantly Higher in RCTs)
    • Agitation: 41.1 vs 9.8 per 1,000 sedations
    • Apnea: 21.5 vs 12.4 per 1,000 sedations
    • Hypoxia: 87.6 vs 40.2 per 1,000 sedations
    • Vomiting: 62.3 vs 16.4 per 1,000 sedations
  • Subclinical Respiratory Depression (Studies that measured capnography, CO2 waveform, or end-tidal CO2)
    • Bradycardia: 20.8 vs 6.5 per 1,000 sedations
    • Hypotension: 32.4 vs 15.2 per 1,000 sedations
    • Hypoxia: 99.7 vs 40.2 per 1,000 sedations
    • Intubation: 6.1 vs 1.6 per 1,000 sedations

Strengths:

• Searched 8 electronic databases
• Adhered to the Preferred Reporting Items for Systematic Reviews (PRISMA) Guidelines
• Used the Cochrane Collaboration bias appraisal tool to assess for bias in RCTs and the Newcastle Ottawa scale to asses for bias in cohort studies
• Tried contacting authors by email if data were missing or unclear
• Interobserver agreement of which studies to include had a kappa of 0.99 (95% CI = 0.98 – 1.0), which is a very high level of agreement. A kappa value of 0.41 – 0.60 would be classified as moderate agreement, 0.61 – 0.80 as substantial agreement, and 0.81 – 1.0 as almost perfect agreement.
• Most studies included had low to moderate risk of biases
• To mitigate some of the limitations of the study, a sensitivity analysis was used based on study design (RCTs), subclinical respiratory depression, and one subgroup analysis based on study definition of hypoxia

Limitations:

• Studies performed on patients <18 years of age were excluded, so results may not generalize to the pediatric population
• Drugs received prior to OSA were not included as interventions, which could cause an increase in adverse events (i.e. respiratory depression from opiates)
• There was high statistical heterogeneity in the outcome of hypoxia and moderate heterogeneity in the outcomes of agitation, hypotension, and vomiting
• Some of the outcomes had variable definitions in different studies, but were classified together as one outcome. For example hypoxia was defined as O2 saturation of less than 85, 90, 92, 93, 94, and 95 depending on which study you were analyzing, but the results were tabulated as a single outcome of hypoxia.
• The authors did the same thing for hypotension, which was defined as a systolic blood pressure < 70mmHg, <90mmHg, and <100mHg, depending on the study analyzed, but the results were tabulated as a single outcome of hypotension.
• Variation in definitions for outcomes and lack of standardization in reporting of outcomes may impact the estimates of this study
• The need for intervention after hypoxia, nausea, and hypotension were not explicitly reported in every study
• There were not enough events in some of the mediation categories to determine if the risk of adverse events was higher with certain mediations or medication combinations

Discussion:

• Data from this systematic review can help in shared decision making to discuss the risks, benefits, and alternatives for PSA
• The routine use of capnography monitoring during PSA is recommended and allows the detection of hypoventilation and apnea earlier than pulse oximetry and/or clinical assessment alone and was indicated in the sensitivity analysis of this study
• ACEP has established their evidence in adult PSA as:
  • Propofol – Level A recommendation
  • Etomidate and Combination Ketamine/Propfol – Level B recommendation
  • Ketamine Alone – Level C recommendation
• Interestingly, the combination of Ketamine/Propofol (Ketofol) incidence of agitation, apnea, hypoxia, bradycardia, hypotension, and vomiting were lower when compared to each medication alone. This should however be balanced with the complexities of mixing two medication together in one syringe, potentially adding steps and calculations leading to medication errors.
• The authors of the paper have also created a pocket card, which they use at their institution based off the data from this paper to help with consent. It can be found along with a link to a video in Data Supplement 9

Author Conclusion: “Serious adverse events during procedural sedation like laryngospasm, aspiration, and intubation are exceedingly rare. Quantitative risk estimates are provided to facilitate shared decision-making, risk communication, and informed consent.”

Clinical Take Home Point: The incidence of serious adverse events during procedural sedation and analgesia in the ED are rare, but shared decision making and informed consent should still be used as this is not a completely benign procedure.

References:

1. Bellolio MF et al. Incidence of Adverse Events in Adults Undergoing Procedural Sedation in the Emergency Department: A Systematic Review and Meta-Analysis. Acad Emerg Med 2016; 23: 119 – 134. PMID: 26801209

For More Thoughts on This Topic Checkout:

• Ryan Radecki at EMLit of Note: When Procedural Sedation Goes Wrong

Post Peer Reviewed By: Anand Swaminathan (Twitter: @EMSwami)