Take Home:

This is essentially a secondary analysis of a previous prospective observational cohort study with high quality methods. The authors have an excellent discussion of the previous studies on this topic (which for those with an interest I highly recommend you read). They conclude that this study supports previous literature which I would think would be seemingly obvious, which is that those who are more ill to begin with have less tolerance of propofol (in a dose-independent relationship) in this and previous studies. Their use of IPTW extends the analysis on this large international population by addressing confounders in a novel way.

Their overall conclusion is that propofol is bad for the critically ill, and especially bad for those with pre-existing risk factors for intubation complications. I agree: This study suggests in even stronger terms that propofol should be used carefully and probably only in unhealthy patients when other options are unavailable.

 

Study Background and Characteristics

• INTUBE study¹ was a prospective cohort study conducted from October 1, 2018, to July 31, 2019
• Enrolled consecutive “critically ill” patients over 8 week period at 197 clinical sites from all over the world. Critically ill was defined as those with “an underlying life-threatening condition causing cardio–respiratory failure or neurologic impairment”.
• Outcome of “cardiovascular instability/collapse” as one or more of the following events within 30 minutes of intubation start: (1199 of 2760 enrolled patients; 43.4%)
  • systolic arterial pressure <65 mm Hg recorded at least once (collapse criteria) – 12.8%
  • cardiac arrest (collapse criteria) – 7.8%
  • systolic arterial pressure <90 mm Hg for >30 minutes – 24%
  • new requirement or increase of vasopressors – 87.8%
  • fluid bolus >15 ml/kg to maintain the target blood pressure – 13.2%
• STROBE Compliant

 

Findings

• CV-instability group were significantly older, high SOFA scores, and higher rates of ischemic heart disase, NYHA 3/4 heart failure, poor oxygenation (SPO2/FIO2 ration), pressors, fluid bolus/total, systolic/diastolic BP, and more commonly respiratory failure and cardiovascular instability as the reason for intubation.
• CV-stability group was less likely to receive propofol and at lower doses and more likely receive ketamine.
• Notably, CV-instability patients were less likely to be intubated by emergency physicians versus anesthesiology.
• Anesthesiologists were more likely to use propofol and more emergency medicine physicians using ketamine.
• Higher incidence of CV-instability in ischemic heart disease and heart failure, noninvasive ventilation and apneic oxygenation, and in the 30–45° head-up position.
• ICU mortality associated with:
  • vasopressors/fluids without hypotension (OR, 1.47; 95% CI, 1.21–1.79)
  • systolic blood pressure <90 mm Hg for >30 min despite vasopressors (OR, 2.65; 95% CI, 1.87–3.75)
  • systolic blood pressure <65 mm Hg (OR, 1.89; 95% CI, 1.31–2.71)
  • cardiac arrest (OR, 8.79; 95% CI, 5.46–14.7)
• Inverse Probability Treatment Weighting² (IPTW) analysis found that the only treatment effect with significance associate with the entire CV-instability group was propofol usage (OR, 1.23; 95% CI, 1.02–1.49).
  • No treatment effect, including propofol use or dosage, was associated with those meeting cardiovascular collapse criteria.

 

References

Russotto V, Tassistro E, Myatra SN, Parotto M, Antolini L, Bauer P, Lascarrou JB, Szu?drzy?ski K, Camporota L, Putensen C, Pelosi P, Sorbello M, Higgs A, Greif R, Pesenti A, Valsecchi MG, Fumagalli R, Foti G, Bellani G, Laffey JG. Peri-intubation Cardiovascular Collapse in Patients Who Are Critically Ill: Insights from the INTUBE Study. Am J Respir Crit Care Med. 2022 Aug 15;206(4):449-458. doi: 10.1164/rccm.202111-2575OC. PMID: 35536310.

1. Russotto V, Myatra SN, Laffey JG, Tassistro E, Antolini L, Bauer P, et al.; INTUBE Study Investigators. Intubation practices and adverse peri-intubation events in critically ill patients from 29 countries. JAMA 2021;325:1164–1172.
2. Nicholas C Chesnaye, Vianda S Stel, Giovanni Tripepi, Friedo W Dekker, Edouard L Fu, Carmine Zoccali, Kitty J Jager, An introduction to inverse probability of treatment weighting in observational research, Clinical Kidney Journal, Volume 15, Issue 1, January 2022, Pages 14–20, https://doi.org/10.1093/ckj/sfab158