Long-term propofol infusion and cardiac failure in adult head-injured patients

doi:10.1016/S0140-6736(00)03547-9

The Lancet

Volume 357, Issue 9250, 13 January 2001, Pages 117-118

https://doi.org/10.1016/S0140-6736(00)03547-9 Get rights and content

Summary

Five adult patients with head injuries inexplicably had fatal cardiac arrests in our neurosurgical intensive-care unit after the introduction of a sedation formulation containing an increased concentration of propofol. To examine the possible relation further, we did a retrospective cohort analysis of head-injured adults admitted to our unit between 1996 and 1999 who were sedated and mechanically ventilated. 67 patients met the inclusion criteria, of whom seven were judged to have died from propofol-infusion syndrome. The odds ratio for the occurrence of the syndrome was 1·93 (95% CI 1·12–3·32, p=0·018) for every mg/kg per h increase in mean propofol dose above 5 mg/kg per h. We suggest that propofol infusion at rates higher than 5 mg/kg per h should be discouraged for long-term sedation in the intensive-care unit.

References (5)

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Propofol infusion syndrome in children
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JP Hanna et al.
Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children
Neurology
(1998)

There are more references available in the full text version of this article.

Cited by (351)

Outcomes of dexmedetomidine versus propofol sedation in critically ill adults requiring mechanical ventilation: a systematic review and meta-analysis of randomised controlled trials
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Citation Excerpt :
As previous studies have suggested a dose-dependent blood pressure response in patients receiving dexmedetomidine sedation with lower doses leading to a decrease in mean arterial pressure and heart rates and higher doses being associated with hypertension,3 we conducted a predefined subgroup analysis by sedative dosage. High dosages were defined as >0.7 μg kg−1 h−1 for dexmedetomidine and ≥5 mg kg−1 h−1 for propofol.25–27 Furthermore, because prior trials including older adults have suggested different treatment effects—especially for ICU LOS and duration of MV—when compared with the general adult population,7,8 we also conducted a predefined subgroup analysis on trials with a mean/median patient age of ≥65 and <65 yr.
Guidelines have recommended the use of dexmedetomidine or propofol for sedation after cardiac surgery, and propofol monotherapy for other patients. Further outcome data are required for these drugs.
This systematic review and meta-analysis was prospectively registered on PROSPERO. The primary outcome was ICU length of stay. Secondary outcomes included duration of mechanical ventilation, ICU delirium, all-cause mortality, and haemodynamic effects. Intensive care patients were analysed separately as cardiac surgical, medical/noncardiac surgical, those with sepsis, and patients in neurocritical care. Subgroup analyses based on age and dosage were conducted.
Forty-one trials (N=3948) were included. Dexmedetomidine did not significantly affect ICU length of stay across any ICU patient subtype when compared with propofol, but it reduced the duration of mechanical ventilation (mean difference −0.67 h; 95% confidence interval: −1.31 to −0.03 h; P=0.041; low certainty) and the risk of ICU delirium (risk ratio 0.49; 95% confidence interval: 0.29–0.87; P=0.019; high certainty) across cardiac surgical patients. Dexmedetomidine was also associated with a greater risk of bradycardia across a variety of ICU patients. Subgroup analyses revealed that age might affect the incidence of haemodynamic side-effects and mortality among cardiac surgical and medical/other surgical patients.
Dexmedetomidine did not significantly impact ICU length of stay compared with propofol, but it significantly reduced the duration of mechanical ventilation and the risk of delirium in cardiac surgical patients. It also significantly increased the risk of bradycardia across ICU patient subsets.
Reply: ST-Segment Elevation, Brugada Syndrome, and Propofol? Is This the Only Thing We Should Be Noticing?
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In vitro alteration on erythrocytes mechanical properties by propofol, remifentanil and vecuronium
2021, Microvascular Research
Several studies report flow disturbance and microcirculation disorders upon anesthesia treatment. These alterations are often related to blood rheology changes. In this work, it was attempted to make a detailed description of the alterations in erythrocyte mechanical properties by the action of propofol, remifentanil, and vecuronium. For this, an in vitro study was performed on red blood cell samples from healthy donors incubated with solutions of propofol (4 μg/mL whole blood), remifentanil (10 ng/mL plasma), and vecuronium (0.15 μg/mL plasma). Erythrocyte viscoelastic parameters were determined by octuplicate using a Reómetro Eritrocitario. Also, a Wilcoxon signed rank-test with Yates correction for continuity was performed to analyze the overall alteration in the mechanical properties of erythrocytes. Statistical analysis showed that the three studied anesthetics changed the erythrocyte mechanical properties at different parts of the membrane. These results would imply an interaction of these anesthetics with the erythrocyte membrane. Finally, this could conduce to alterations in microcirculation.
Maternal and neonatal wellbeing during elective C-section induced with a combination of propofol and dexmedetomidine: How effective is the placental barrier in dogs?
2019, Theriogenology
Anaesthetics administered during C-section (CS) can cross the placenta and the foetal blood-brain barrier contributing to distress up to neonatal mortality. Therefore, to prevent neonatal risks, sedatives and analgesics are not commonly administered to the bitch until all pups are delivered. This study aims to evaluate the effect of a new anaesthetic and analgesic protocol for elective CS in dogs, focused on both maternal and neonatal wellbeing. General anaesthesia was induced by a combination of propofol (PPF) and dexmedetomidine (DEX) and maintained with isoflurane. DEX was added to PPF in order to provide analgesia and to reduce PPF dose. Propofol and DEX concentrations in maternal blood, amniotic fluid, and placenta were correlated to maternal and neonatal parameters. Maternal pain score was assessed with Glasgow Composite Measure Pain Scale short-form. Nine healthy purebred dogs scheduled for elective CS delivered 54 pups. The 77.8% of pups were vigorous at birth and assigned to the highest Apgar score (AS). The lowest AS was recorded in pups from mothers receiving additional doses of PPF (p < 0.001). Apgar scores improved with the increase in time between induction and pups' extraction, starting from 30 min after induction (p < 0.01). This study could contribute to clarify the controversy about the optimal extraction's time of pups after induction i.e. the best time between PPF administration and birth. No bitch showed post-operative pain or required additional analgesic doses based on their pain score. Maternal blood PPF and DEX, as well as placental PPF concentrations, decreased over time (p < 0.01). Conversely, placental DEX was fair uniformly detected in littermate pups. Both PPF and DEX were not detectable in amniotic fluid. Placenta resulted an effective barrier against foetal DEX exposure, making this protocol safe, analgesic and advisable for elective CS in dogs.
Propofol infusion syndrome: a structured literature review and analysis of published case reports
2019, British Journal of Anaesthesia
Citation Excerpt :
The first reported adult death attributed to propofol infusion syndrome occurred in 1998.35 In 2001, Cremer and colleagues11 published a review of adults who died in a neurointensive care unit after being admitted with a head injury: seven of their deaths were attributed to propofol infusion syndrome. Subsequently, the literature has been dominated by adult cases.
Propofol infusion syndrome is a rare, potentially fatal condition first described in children in the 1990s and later reported in adults. We provide a narrative review of what is currently known about propofol infusion syndrome, including a structured analysis of all published case reports; child and adult cases were analysed separately as propofol is no longer used for long-term sedation in children. The review contains an update on current knowledge of the pathophysiology of this condition along with recommendations for its diagnosis, prevention, and management. We reviewed 108 publications documenting 168 cases of propofol infusion syndrome. We evaluated clinical features and analysed factors influencing mortality in child and adult cases using separate multivariate analysis models. We used separate multiple linear regression models to analyse relationships between cumulative dose of propofol and the number of features seen and organ systems involved. Lipidaemia, fever, and hepatomegaly occurred more frequently in children than in adults, whilst rhabdomyolysis and hyperkalaemia were more frequent in adults. Mortality from propofol infusion syndrome is independently associated with fever and hepatomegaly in children, and electrocardiogram changes, hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol infusion rate >5 mg kg⁻¹ h⁻¹ in adults. The cumulative dose of propofol was associated with an increased number of clinical features and the number of organ systems involved in adult cases only. Clinicians should consider propofol infusion syndrome in cases of unexplained metabolic acidosis, ECG changes, and rhabdomyolysis. We recommend early consideration of continuous haemofiltration in the management of propofol infusion syndrome.
Pharmacokinetics and Pharmacology of Drugs Used in Children
2019, A Practice of Anesthesia for Infants and Children
The pharmacokinetics (PK) and pharmacodynamics (PD) of most medications in children especially neonates, differ from those in adults. Children exhibit different PK and PD from adults because of their immature renal and hepatic function, different body composition, altered protein binding, distinct disease spectrum, diverse behavior, and dissimilar receptor patterns. PK differences necessitate modification of the dose and the interval between doses to achieve the desired concentration associated with a clinical response and to avoid toxicity. In addition, some medications may displace bilirubin from its protein binding sites and possibly predispose to kernicterus in premature neonates. Drug effect may be influenced by altered capacity of the end organ, such as the heart or bronchial smooth muscle, to respond to medications in children compared with adults. In this chapter we discuss basic pharmacologic principles as they relate to drugs commonly used by anesthesiologists.

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Fast track — Research LettersLong-term propofol infusion and cardiac failure in adult head-injured patients

Summary

Propofol infusion syndrome in children

Paediatr Anaesth

Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children

Neurology

Fast track — Research Letters
Long-term propofol infusion and cardiac failure in adult head-injured patients