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.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction and purpose
Since people have been conducting surgeries to improve their health, they have always faced the problem of pain that these actions inevitably bring. Propofol as an anesetic ...is one of the solutions to these problems. Due to the widespread use of this drug, its side effects are often observed. This paper aims to gather the available knowledge about the adverse reactions of propofol in clinical practice and to present ways to reduce the risk of their occurrence described in the literature.
Material and methods
The following review of the work was based on viewable data obtained from the PubMed database and Google Scholar. The key words used in the search were: propofol, propofol infiusion syndrome, propofol bradycardia, propofol infusion pain, propofol neuroprotection, propofol hypotension.
Conclusions
Studies indicate a number of possible solutions to reduce the risk or intensity of individual side effects. . There are many possibilities, both pharmacological and non-pharmacological, fulfilling this task – administration of propofol simultaneously with drugs of other groups responsible for sedation, replacement of propofol with another sedation drug in selected situations, cold compresses, analgetic usage of vibrations. These methods require further research and the development of appropriate protocols for use in clinical situations.
Pharmacokinetic (PK) and pharmacodynamic (PD) models are used in target-controlled-infusion (TCI) systems to determine the optimal drug administration to achieve a desired target concentration in a ...central or effect-site compartment. Our aim was to develop a PK–PD model for propofol that can predict the bispectral index (BIS) for a broad population, suitable for TCI applications.
Propofol PK data were obtained from 30 previously published studies, five of which also contained BIS observations. A PK–PD model was developed using NONMEM. Weight, age, post-menstrual age (PMA), height, sex, BMI, and presence/absence of concomitant anaesthetic drugs were explored as covariates. The predictive performance was measured across young children, children, adults, elderly, and high-BMI individuals, and in simulated TCI applications.
Overall, 15 433 propofol concentration and 28 639 BIS observations from 1033 individuals (672 males and 361 females) were analysed. The age range was from 27 weeks PMA to 88 yr, and the weight range was 0.68–160 kg. The final model uses age, PMA, weight, height, sex, and presence/absence of concomitant anaesthetic drugs as covariates. A 35-yr-old, 170 cm, 70 kg male (without concomitant anaesthetic drugs) has a V1, V2, V3, CL, Q2, Q3, and ke0 of 6.28, 25.5, 273 litres, 1.79, 1.75, 1.11 litres min−1, and 0.146 min−1, respectively. The propofol TCI administration using the model matches well with recommendations for all age groups considered for both anaesthesia and sedation.
We developed a PK–PD model to predict the propofol concentrations and BIS for broad, diverse population. This should be useful for TCI in anaesthesia and sedation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABA
) receptors to dampen neuronal activity in the brain
. However, direct ...structural information on the mechanisms of general anaesthetics at their physiological receptor sites is lacking. Here we present cryo-electron microscopy structures of GABA
receptors bound to intravenous anaesthetics, benzodiazepines and inhibitory modulators. These structures were solved in a lipidic environment and are complemented by electrophysiology and molecular dynamics simulations. Structures of GABA
receptors in complex with the anaesthetics phenobarbital, etomidate and propofol reveal both distinct and common transmembrane binding sites, which are shared in part by the benzodiazepine drug diazepam. Structures in which GABA
receptors are bound by benzodiazepine-site ligands identify an additional membrane binding site for diazepam and suggest an allosteric mechanism for anaesthetic reversal by flumazenil. This study provides a foundation for understanding how pharmacologically diverse and clinically essential drugs act through overlapping and distinct mechanisms to potentiate inhibitory signalling in the brain.
Full text
Available for:
FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Pain on propofol injection (POPI) is a minor problem that all anesthetists face every day. Introduction of several new formulations and hundreds of clinical trials have failed to find its remedy with ...just one intervention in all patients. This article highlights the causes of POPI and interventions that are used to eliminate this pain in current practice. Relevant articles from Medline and Embase databases were searched and included in this descriptive review with the following conclusions: (1) POPI is due to irritation of venous adventitia leading to release of mediators such as kininogen from kinin cascade. (2) When two or more drugs or measures are used, the incidence of POPI decreases considerably. Hence, the approach to eliminating POPI should be multimodal. (3) Any regimen that includes a drug having local anesthetic effect combined with central sedative/analgesic and rapid injection into a large vein should definitely reduce the risk of POPI to negligible levels.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Peri-intubation hypotension is associated with increased hospital length of stay and morbidity. Propofol is associated with alterations in hemodynamics. We hypothesize that using propofol for ...induction leads to peri-intubation hypotension in trauma critical care patients.
Patients that underwent unplanned intubation in the trauma intensive care unit (TICU) were prospectively enrolled. Peri-intubation vitals and medications were recorded to assess hypotension within 10 min of intubation. Patients were divided into propofol (PROP) or other medication (OTR) groups.
Data was complete for 69 patients; 31 PROP and 38 OTR. In OTR there was an 8.8-point (−21.1, 3.6) SBP decrease (p = 0.159) and in PROP there was a 30.8-point (−45.6, −16.0) SBP decrease (p = 0.0002) with significant increases in heart rate (HR) and shock index (SI) (HR p = 0.001, SI p < 0.0001).
In patients without hypotension prior to intubation, we observed a statistically significant drop in the patients’ SBP with use of propofol. In trauma critical care unit patients, we recommend considering an induction medication for unplanned intubation other than propofol.
•Propofol has been associated with peri-intubation hemodynamic instability.•Induction agents for unplanned intubation have not been specifically studied in trauma critical care patients.•When propofol is administered over other medications for unplanned intubation, there is a drop in systolic blood pressure.•There is an increase in heart rate and shock index when administering propofol over other intubation induction medications.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter ...γ-aminobutyric acid (GABA) at the GABA
A
receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers’ knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and Aim
Since 2008, there exists a German S3‐guideline allowing non‐anesthesiological administration of propofol for gastrointestinal endoscopy. In this prospective, national, multicenter ...study, we evaluated the safety of endoscopist‐administered propofol sedation (EDP) in German outpatient practices of Gastroenterology.
Methods
In this multicenter survey of 53 ambulatory practices of Gastroenterology, we prospectively evaluated 24 441 patients that had received EDP. We recorded adverse events during the endoscopic procedure and additionally retrieved questionnaires investigating subjective parameters 24 h after the endoscopic procedure.
Results
In 24 441 patients 13 793 colonoscopies, 6467 esophagogastroduodenoscopies, and 4181 double examinations were performed. In this study, 52.1% of the patients received propofol mono‐sedation, and 47.9% received a combination of midazolam and propofol. Major adverse events occurred in four patients (0.016%) enrolled to this study (three mask ventilations and one laryngospasm). Minor adverse events were observed in 112 patients (0.46%) with hypoxemia being the most common minor event. All patients with adverse events recovered without persistent impairment. Minor adverse events occurred more frequently in patients sedated with propofol mono compared to propofol and midazolam (P < 0.0001) and correlated with increasing propofol dosages (P < 0.001; Pearson correlation coefficient r = 0.044). Twenty‐four hours after the endoscopy, patients sedated with propofol plus midazolam stated a significantly reduced sensation of pain (P < 0.01) and improved symptoms of dizziness, nausea and vomiting (P < 0.001) compared to patients having received propofol mono‐sedation.
Conclusion
Four years after the implementation of a German S3‐Guideline for endoscopic sedation, we demonstrated that EDP is a safe procedure.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
