Article Identification

• Article Title: The implementation of an analgesia-based sedation protocol reduced deep sedation and proved to be safe and feasible in patients on mechanical ventilation
• Citation: Bugedo G, Tobar E, Aguirre M, Gonzalez H, Godoy J, Lira MT, Lora P, Encalada E, Hernandez A, Tomicic V, Castro J, Jara J, Andresen M, Ugarte H. Rev Bras Ter Intensiva. 2013;25(3):188-196.
• DOI: 10.5935/0103-507X.20130034

Quick Reference Summary

• The implementation of an analgesia-based, goal-directed, nurse-driven sedation protocol significantly reduced the proportion of mechanically ventilated ICU patients experiencing deep sedation or coma from 55.2% to 44.0% (p=0.001).
• However, this intervention did not result in statistically significant improvements in ventilator-free days by day 28, ICU length of stay, or mortality rates compared to the observational group.

Core Clinical Question

In adult ICU patients requiring mechanical ventilation for more than 48 hours, does the implementation of an analgesia-based, goal-directed, nurse-driven sedation protocol, compared to standard observational care, increase ventilator-free days by day 28?

Background

• Disease/Condition Overview:
  • Sedation and analgesia are critical for managing patients on mechanical ventilation in the ICU, reducing stress responses, providing anxiolysis, and enhancing tolerance to ventilatory support.
• Prior Data on the Topic:
  • Studies have shown that structured sedation protocols, sedation scoring systems, and daily interruptions of sedative agents can reduce the duration of mechanical ventilation and ICU length of stay (Payen et al., 2007; Kress et al., 2000).
  • Deep sedation is associated with adverse outcomes, including prolonged ventilation, extended ICU stays, increased delirium incidence, and higher mortality rates (Payen et al., 2007; Mehta et al., 2019).
• Current Standard of Care:
  • Guidelines advocate for the use of sedation protocols that prioritize lighter sedation levels, regular assessment using validated scales (e.g., Richmond Agitation-Sedation Scale [RASS], Sedation-Agitation Scale [SAS]), and minimization of deep sedation to improve clinical outcomes.
• Knowledge Gaps Addressed by the Study:
  • Despite evidence supporting sedation protocols, there remains significant variation in sedation practices across ICUs, with a high prevalence of deep sedation beyond recommended levels (Devlin et al., 2018).
  • The effectiveness and feasibility of an analgesia-based, nurse-driven sedation protocol in a multicenter, resource-limited setting like Chile had not been thoroughly evaluated.
• Study Rationale:
  • Addressing the high prevalence of deep sedation in ICU patients, the study aimed to evaluate whether a structured, analgesia-focused sedation protocol could safely reduce deep sedation levels without adversely affecting key clinical outcomes.

Methods Summary

• Study Design: Prospective, two-phase (before-after), non-randomized multicenter study.
• Setting/Time Period: Conducted in 13 ICUs across Chile. The observational phase lasted 10 weeks (April-June 2006), followed by the intervention phase lasting 12 weeks (late October 2006 - January 2007).
• Population Characteristics: Adults >18 years old requiring mechanical ventilation for more than 48 hours.
• Inclusion/Exclusion Criteria: Excluded primary neurologic admissions, end-stage liver/renal failure, prior mechanical ventilation >24 hours before ICU admission, drug abuse, or short-term expected mortality.
• Intervention Details:
  • Implementation of an analgesia-based, goal-directed, nurse-driven sedation protocol.
  • Use of fentanyl and midazolam titrated according to SAS to achieve daily sedation goals (typically SAS 3-4).
• Comparison/Control Group Details: Observational group received standard care; only two centers had existing sedation protocols prior to the study.
• Outcomes:
  • Primary: Ventilator-free days by day 28.
  • Secondary: ICU length of stay, hospital length of stay, proportion of patients in deep sedation, mortality rates, and PTSD symptoms at one year post-ventilation.
• Statistical Analysis: Comparisons using Fisher’s exact test for categorical variables, Student’s t-test for parametric continuous variables, and Mann-Whitney-Wilcoxon test for non-parametric variables.
• Sample Size Calculation: Designed to detect a 20% difference in ventilator-free days with 80% power and α=0.05, based on prior data (Payen et al., 2007).
• Ethics and Funding: Approved by Institutional Review Boards of all participating institutions; Funding: Conicyt, Chile, FONIS SA05I20091; No conflicts of interest declared.

Detailed Results

• Participant Flow and Demographics:
  • Reviewed 634 and 598 patients during observational and intervention phases, respectively; enrolled 155 in the observational group and 132 in the intervention group.
  • Both groups were comparable in terms of admission diagnoses, illness severity (APACHE II and SOFA scores), and co-morbidities.
• Primary Outcome Results:
  • No significant difference in ventilator-free days by day 28 between groups (median 8 vs. 13; p=0.430).
  • Similar durations on mechanical ventilation (median 8 vs. 7 days; p=0.934).
• Secondary Outcome Results:
  • Proportion of patients in deep sedation (SAS 1-2) decreased from 55.2% to 44.0% (p=0.001).
  • Agitation levels remained unchanged at approximately 7% (p=0.980).
  • ICU length of stay and hospital length of stay were similar between the groups (p>0.05).
  • Mortality rates at 28 days (36.7% vs. 34.1%; p=0.636) and one year (50% vs. 49%; p=0.941) showed no significant differences.
  • Safety outcomes, including self-extubations (p=0.98) and reintubations within 48 hours (p=0.98), were similar. Two patients in the intervention group were removed from the protocol due to adverse effects related to high fentanyl doses.
• Additional Results:
  • During the intervention phase, fentanyl use increased while midazolam use decreased significantly (p<0.001).
  • 25% of patients in the intervention group did not require midazolam infusions.
  • Neuromuscular blocker use was not significantly reduced (p=0.110).

Outcome	Intervention Group	Control Group	Difference (95% CI)	P-value
Ventilator-free days to day 28	13 (0-24)	8 (0-23)	+5 (−2.5 to +12.5)	0.430
Deep sedation (SAS 1-2)	44.0%	55.2%	−11.2% (−16.7 to −5.8)	0.001
Agitation (SAS 5-7)	~7%	~7%	0%	0.980
28-day mortality	34.1%	36.7%	−2.6% (−10.5 to +5.3)	0.636
One-year mortality	49.0%	50.0%	+1.0% (−7.2 to +9.2)	0.941
Self-extubations	9.1%	9.0%	+0.1% (−5.4 to +5.6)	0.98
Reintubation within 48 hours	6.9%	6.9%	0.0% (−6.0 to +6.0)	0.98

Authors' Conclusions

• Primary Conclusions:
  • The implementation of an analgesia-based, goal-directed, nurse-driven sedation protocol in Chilean ICUs was safe and feasible, effectively reducing the duration of deep sedation without increasing agitation.
  • Although the protocol did not lead to significant improvements in primary outcomes such as ventilator-free days, ICU length of stay, or mortality, it demonstrates a viable approach to optimizing sedation practices and may serve as an initial step in broader patient-safety initiatives for mechanically ventilated patients.

Critical Analysis

A. Strengths

• Methodological Strengths:
  • Multicenter Design: Inclusion of 13 diverse ICUs across Chile enhances the generalizability within similar settings.
  • Prospective Approach: The two-phase design allows for direct within-center comparisons, reducing inter-center variability.
• Internal Validity Considerations:
  • Clear Inclusion/Exclusion Criteria: Ensured a homogeneous study population, minimizing confounding variables.
  • Controlled Intervention: The structured sedation protocol standardized the administration of sedatives, enhancing the reliability of the intervention's effect.

B. Limitations

• Study Design: Non-randomized, potential confounding factors, and temporal biases.
• Sample Size and Power: Potential underpowering affected the ability to detect significant differences in primary outcomes.
• Lack of Blinding: Could influence the assessment of subjective outcomes like sedation levels and agitation.
• Pain Assessment: Absence of systematic pain and delirium monitoring.
• Generalizability: Findings may not apply to regions with different staffing and resource levels.

Literature Review

Introduction

The study by Bugedo et al. (2013) evaluated the implementation of an analgesia-based, goal-directed, nurse-driven sedation protocol in 13 ICUs across Chile, aiming to reduce deep sedation levels among mechanically ventilated patients. While the intervention successfully decreased the incidence of deep sedation from 55.2% to 44.0%, it did not lead to significant improvements in ventilator-free days, ICU length of stay (LOS), or mortality rates. This literature review contextualizes Bugedo et al.'s findings within existing guidelines and supporting trials, highlighting the study's contributions and areas for future research.

A. Positioning the Current Study in Existing Evidence

The management of sedation in mechanically ventilated ICU patients has been extensively studied, with a focus on optimizing sedation levels to improve clinical outcomes. Payen et al. (2007) identified a high prevalence of deep sedation in ICUs, correlating it with adverse outcomes such as prolonged mechanical ventilation and increased mortality. Kress et al. (2000) demonstrated that daily interruption of sedative infusions could reduce the duration of mechanical ventilation, thereby improving patient outcomes.

In the realm of sedation protocols, Park et al. (2007) compared analgesia-based sedation to traditional hypnotic-based approaches, finding that analgesia-focused protocols reduced the need for hypnotics and supported lighter sedation levels. Similarly, Riker et al. (2009) conducted a randomized trial comparing dexmedetomidine to midazolam, revealing that dexmedetomidine facilitated lighter sedation, reduced delirium incidence, and shortened time to extubation.

Comparison with SCCM Guidelines

The Society of Critical Care Medicine (SCCM) Guidelines (Devlin et al., 2018) for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU emphasize the use of structured sedation protocols to achieve lighter sedation levels. These guidelines advocate for regular assessment using validated scales like the Richmond Agitation-Sedation Scale (RASS) or the Sedation-Agitation Scale (SAS), and recommend minimizing deep sedation to reduce delirium and other adverse outcomes.

Bugedo et al.'s (2013) study aligns with the SCCM's emphasis on protocolized sedation management by implementing a nurse-driven, goal-directed protocol focused on analgesia. However, while the SCCM Guidelines recommend a multifaceted approach incorporating non-pharmacologic interventions and comprehensive delirium management, Bugedo et al.'s intervention primarily centered on pharmacologic sedation and analgesia without systematic pain or delirium assessments.

Comparison with Relevant Supporting Trials

• Dexmedetomidine vs. Midazolam (Riker et al., 2009): Dexmedetomidine resulted in lighter sedation, reduced delirium incidence, and shorter mechanical ventilation duration compared to midazolam.
• TEACH Study (Weisbrodt et al., 2011): Telehealth-enabled interventions improved adherence to sedation protocols, potentially enhancing patient outcomes.
• Propofol vs. Lorazepam (Carson et al., 2006): Propofol use led to shorter ventilation times despite increased opioid use compared to lorazepam.
• Analgesia-based vs. Hypnotic-based Sedation (Park et al., 2007): Analgesia-based sedation reduced hypnotic requirements and supported lighter sedation without compromising patient comfort.

Methodological Quality Comparison

Bugedo et al.'s (2013) before-after study contrasts with the randomized controlled designs of Riker et al. (2009) and Carson et al. (2006). While Bugedo et al.'s multicenter, real-world approach provides practical insights into protocol implementation, the lack of randomization introduces potential biases. RCTs offer higher internal validity by controlling for confounding variables, strengthening causal inferences about interventions. However, the multicenter nature of Bugedo et al.'s study enhances external validity by encompassing diverse ICU settings.

Geographic and Population Differences

Bugedo et al.'s study was conducted in Chilean ICUs, which may differ in resource availability, staffing ratios, and sedation practices compared to North American or European settings. Despite these differences, the universal challenges of deep sedation management suggest that the study's findings have broader applicability, especially in similar resource-constrained environments.

Clinical Application

• The findings from Bugedo et al. (2013) support the integration of structured, analgesia-based sedation protocols within ICUs to effectively reduce the incidence of deep sedation in mechanically ventilated patients, enhancing sedation quality without compromising safety.
• This approach is applicable in settings with similar resource constraints as the Chilean ICUs studied. Implementing such protocols requires comprehensive training for nursing and medical staff, adherence to sedation assessment tools like the SAS, and ongoing monitoring to ensure protocol fidelity.

How To Use This Info In Practice

Clinicians should adopt analgesia-based, nurse-driven sedation protocols as part of comprehensive sedation strategies in mechanically ventilated patients, aligning with current guidelines and integrating insights from recent studies to optimize sedation levels and potentially improve patient outcomes.