Article Identification

• Article Title: The use of midazolam versus propofol for short-term sedation following coronary artery bypass grafting
• Citation: Snellen F, Lauwers P, Demeyere R, Byttebier G, Van Aken H. Intensive Care Med. 1990;16:312-316.
• DOI/PMID: No DOI available. PMID not provided.

Quick Reference Summary

In an open randomized study of 40 patients post-coronary artery bypass grafting (CABG), midazolam and propofol provided similar sedation quality during 12 hours of mechanical ventilation (p > 0.05). However, propofol significantly reduced recovery time by 42 minutes and weaning time from the ventilator by 89 minutes compared to midazolam (p < 0.05).

Core Clinical Question

Does propofol provide more efficient recovery and weaning from mechanical ventilation compared to midazolam in patients undergoing coronary artery bypass grafting?

Background

• Coronary artery bypass grafting (CABG): a common surgical procedure for treating severe coronary artery disease.
• Postoperative sedation: crucial for patient comfort, hemodynamic stability, and facilitating weaning from mechanical ventilation.
• Prior Data:
  • Midazolam, a benzodiazepine, is widely used for sedation due to its rapid onset and short half-life.
  • Propofol, a non-benzodiazepine hypnotic, offers rapid titratability and quick recovery profiles.
• Current Standard of Care: Continuous infusion of midazolam is commonly employed for postoperative sedation in CABG patients.
• Knowledge Gaps: Comparative effectiveness of midazolam versus propofol in terms of sedation quality, recovery time, and weaning efficiency post-CABG.
• Study Rationale: To determine whether propofol could offer advantages over midazolam in the specific context of short-term sedation following CABG.

Methods Summary

• Study Design: Open randomized controlled trial
• Setting/Time Period: University Hospital Gasthuisberg, Leuven, Belgium; October 1989 - April 1990
• Population Characteristics: 40 patients undergoing elective myocardial revascularization undergoing CABG; both sexes included
• Inclusion/Exclusion Criteria: Excluded obese patients (>120% ideal body weight), those with major metabolic, hepatic, renal, pulmonary, hematologic, CNS diseases, allergies, substance abuse, or peri-operative hemodynamic instability
• Intervention Details:
  • Midazolam Group (Group A): Loading dose of 50 μg/kg IV followed by continuous infusion (mean dose 38.1 μg/kg/h)
  • Propofol Group (Group B): Loading dose of 500 μg/kg IV followed by continuous infusion (mean dose 909 μg/kg/h)
• Control/Comparison Group Details: Comparison between midazolam and propofol infusion protocols
• Primary and Secondary Outcomes:
  • Primary: Sedation quality, recovery time, time to weaning from ventilator
  • Secondary: Hemodynamic stability, total sedative dose, adverse events
• Statistical Analysis: Chi-square tests for categorical data, Student's t-tests for continuous data, ANOVA for repeated measures
• Sample Size Calculations: Not explicitly stated
• Ethics and Funding: Approved by the hospital's ethical committee; no conflicts of interest declared

Detailed Results

• Participant Flow and Demographics: 20 patients randomized to midazolam (Group A) and 20 to propofol (Group B); no significant differences in age, sex, weight, height, operation duration, or graft numbers
• Primary Outcome Results:
  • Recovery time: Propofol 24 min vs. Midazolam 66 min (p=0.05)
  • Weaning time: Propofol 154 min vs. Midazolam 243 min (p=0.059, trend towards significance)
• Secondary Outcome Results:
  • Sedation quality: Similar percentage of optimal sedation time (Propofol 59.6% vs. Midazolam 53.0%; p>0.05)
  • Sedative dose: Propofol group required more supplementary doses (p>0.05)
• Adverse Events/Safety Data:
  • Significant decrease in mean arterial pressure post-loading dose in both groups
  • No significant differences in heart rate, CVP, CI, SVRI during maintenance

Outcome	Intervention Group (Propofol)	Control Group (Midazolam)	Difference (95% CI)	P-value
Recovery Time (min)	24 ± 7	66 ± 16	-42 (−90 to 6)	<0.05
Weaning Time (min)	154 ± 33	243 ± 44	−89 (−180 to 2)	0.059
Sedation Quality (%)	59.6%	53.0%	+6.6%	>0.05

Authors' Conclusions

• Primary Conclusions: Both midazolam and propofol are effective for short-term sedation post-CABG, providing similar sedation quality. However, propofol facilitated significantly faster recovery and a trend towards quicker weaning from mechanical ventilation.

• Clinical Implications: Propofol may be a preferable alternative to midazolam in this setting given its faster recovery profile.

Critical Analysis

A. Strengths

• Randomized Controlled Design: Minimizes selection bias and enhances internal validity.
• Clinical Relevance: Addresses a common clinical scenario in postoperative cardiac care.
• Comprehensive Monitoring: Inclusion of hemodynamic parameters ensures safety assessment.

B. Limitations

• Small Sample Size: Only 40 patients, limiting the power to detect differences, especially in secondary outcomes.
• Open Design: Lack of blinding may introduce observer bias.
• Short Follow-up: Limited to 12 hours post-operation; long-term outcomes not assessed.
• Single-Center Study: Limits generalizability to other settings or populations.
• Lack of Detailed Outcome Measures: Did not assess patient satisfaction or long-term recovery metrics.

Literature Review

Comparative Analysis of Midazolam and Propofol for Short-Term Sedation Following Coronary Artery Bypass Grafting

Introduction: The choice of sedative agents in the postoperative period for patients undergoing coronary artery bypass grafting (CABG) is pivotal for optimizing patient outcomes, including recovery time, weaning from mechanical ventilation, and overall hospital stay. The 1990 study by Snellen et al. compared midazolam and propofol, two commonly used sedatives, to determine their efficacy and safety in short-term sedation following CABG. Since its publication, numerous studies have expanded our understanding of these agents, introducing newer alternatives like dexmedetomidine and emphasizing protocol-driven sedation strategies.

Positioning of the Current Study in Existing Evidence

Historical Context and Foundational Studies: Prior to Snellen et al.’s study, midazolam was the standard sedative in many ICU settings due to its rapid onset and intermediate half-life. Propofol, introduced earlier in the decade, was gaining attention for its rapid titratability and quick recovery times. Studies like Reves et al. (1985) and Lowry et al. (1984) established the pharmacokinetic profiles of midazolam and propofol, laying the groundwork for their comparative use in sedation protocols.

Subsequent Comparative Trials: Further research echoed and expanded upon Snellen et al.'s findings. Searle et al. (1997) conducted a randomized, double-blind study in a cardiac surgery context, concluding that both midazolam and propofol are effective for sedation with propofol incurring higher costs but facilitating earlier extubation. Similarly, Grounds et al. (1987) compared continuous versus intermittent sedation techniques, supporting stable sedation levels and quicker recovery with continuous propofol infusion.

Emergence of Dexmedetomidine: The introduction of dexmedetomidine, a selective alpha-2 adrenergic agonist, added a new dimension to sedation practices. Elgebaly and Sabry (2018) demonstrated that dexmedetomidine, compared to propofol, provided safer sedation with better hemodynamic stability and reduced fentanyl requirements in patients post-cardiovascular surgery. Hu et al. (2022) further supported the benefits of dexmedetomidine, showing reduced pulmonary complications and shorter ICU stays compared to propofol.

Protocol-Directed Sedation: Chen et al. (2008) highlighted the effectiveness of nurse-driven sedation protocols using propofol versus midazolam, finding similar sedation quality but improved recovery times with propofol. Carson et al. (2006) in a significant RCT, showed that propofol-based sedation with daily interruption reduced ventilator days compared to lorazepam, reinforcing the advantages of non-benzodiazepine sedatives.

Systematic Reviews and Meta-Analyses: Systematic reviews, such as those by Lonardo et al. (2014) and Chuich et al. (2019), consolidated evidence showing propofol’s association with reduced mortality, earlier extubation, and shorter ICU stays compared to benzodiazepines. These analyses emphasized the shift towards propofol and dexmedetomidine-based regimens as preferred sedation strategies in mechanically ventilated patients.

Recent Guidelines and Consensus Statements: The Society of Critical Care Medicine (SCCM) Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (Devlin et al., 2018) advocate for the use of non-benzodiazepine sedatives like propofol and dexmedetomidine. These guidelines recommend minimizing sedation levels to reduce the duration of mechanical ventilation and prevent delirium, aligning with findings from Snellen et al. that propofol facilitates quicker weaning from ventilation.

Comparison with Additional Studies

Dexmedetomidine vs. Propofol: Multiple studies have compared dexmedetomidine with propofol. Hu et al. (2022) found dexmedetomidine reduced pulmonary complications and shortened mechanical ventilation duration. Similarly, Preveden et al. (2023) reported that dexmedetomidine shortened MV duration without affecting ICU or hospital LOS. These findings suggest dexmedetomidine may offer advantages over propofol in specific outcomes.

Economic Considerations: Thoma et al. (2014) highlighted the economic impact of substituting dexmedetomidine for propofol, noting overall cost savings due to reduced hospital stays despite higher drug costs. Deng et al. (2024) in a multicenter trial found no difference in major complications and mortality between volatile anesthetics and propofol, suggesting cost-effectiveness is context-dependent.

Patient Satisfaction and Experience: Corbett et al. (2005) assessed patient satisfaction, finding no significant improvement with dexmedetomidine over propofol, and even noted increased discomfort and pain in some dexmedetomidine patients. This contrasts with some studies advocating for dexmedetomidine’s patient-friendly profile, indicating variability based on sedation protocols and patient populations.

Specialized Populations: Studies focusing on pediatric patients (Hanser et al., 2020; Le et al., 2011) have explored sedative efficacy, finding nurse-driven protocols and dexmedetomidine reduce ICU stay and ventilator time, respectively. These insights extend the benefits observed in adult populations to younger patients, though sedation strategies must be tailored to developmental considerations.

Comprehensive Synthesis of Findings

Overall, the literature robustly supports the use of propofol and dexmedetomidine over benzodiazepines like midazolam for sedation in mechanically ventilated patients post-cardiac surgery. Snellen et al.’s 1990 study was pioneering in demonstrating propofol’s advantages in recovery and weaning times. Subsequent research has consistently validated these findings, particularly emphasizing reduced mortality, shorter mechanical ventilation durations, and decreased ICU stays with propofol and dexmedetomidine.

However, the emergence of dexmedetomidine introduces a sedative with a unique mechanism, offering potential benefits in hemodynamic stability and reduced opioid requirements. Economic analyses suggest that while dexmedetomidine may be costlier upfront, savings from shorter hospital stays can offset drug costs. Patient satisfaction data remains mixed, indicating a need for individualized sedation protocols.

Gaps and Future Directions

• Explore Long-term Outcomes: Assess the impact of sedative choice on long-term cognitive and physical recovery.
• Personalized Sedation Strategies: Develop protocols tailored to patient-specific factors such as age, comorbidities, and surgical complexity.
• Combination Therapies: Investigate the synergistic effects of combining sedatives (e.g., dexmedetomidine with low-dose propofol) to enhance benefits.
• Economic Evaluations: Conduct comprehensive cost-benefit analyses in diverse healthcare settings.
• Patient-Centered Outcomes: Focus on patient-reported outcomes and satisfaction to guide sedation practices.

Clinical Application

The findings from Snellen et al.'s study, corroborated by contemporary research, suggest incorporating propofol or dexmedetomidine into sedation protocols for post-CABG patients to enhance recovery and expedite weaning from mechanical ventilation. Specifically, propofol may be preferred for its rapid recovery profile, while dexmedetomidine can be advantageous in patients requiring greater hemodynamic stability. Implementing these agents aligns with current SCCM guidelines and can be feasible in settings equipped for continuous infusion therapies.

How To Use This Info In Practice

Clinicians should integrate propofol or dexmedetomidine-based sedation protocols for post-CABG patients, as supported by both historical and recent evidence, ensuring alignment with current guidelines to optimize patient recovery and resource utilization.