Anesthetic agents: Intravenous
Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor in Manual of Neuroanesthesia, 2017
The clinically recommended dosage and pharmacokinetics of propofol are summarized in Table 19.2. The induction dose of propofol in a healthy individual is 1.5–2.5 mg/kg. Because of its short half-life, propofol can also be used as total intravenous anesthesia in maintenance of anesthesia. The maintenance dose of propofol in patients <55 years is 0.1–0.2 mg/kg/min and in patients >55 years, it is 0.05–0.1 mg/kg. Recovery after propofol infusion or multiple doses is much faster than that after barbiturates.11 In patients receiving propofol for prolonged duration, there is increased risk of developing “propofol infusion syndrome,” which is a rare medical condition. It usually develops if infusion is continued for more than 48 h at a dose of 4 mg/kg/h.12 This potentially lethal metabolic derangement has been more commonly found in children and critically ill patients on prolonged infusion of high-dose substance in combination with catecholamines or corticosteroids.13 The signs and symptoms of propofol infusion syndrome include rhabdomyolysis, metabolic acidosis, cardiac failure, and renal failure.12,14,15
Systemic care—Renal, hematologic, gastrointestinal
Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor in Essentials of Anesthesia for Neurotrauma, 2018
Medication nephrotoxicity. Radiocontrast agents and potential nephrotoxic medications, including antibiotics, propofol, mannitol, and hypertonic saline, are commonly used in NICU patients. Propofol, a popular sedative agent in the ICU, can cause propofol infusion syndrome when high doses and/or prolonged duration are administered. The manifestations of propofol infusion syndrome include cardiac arrhythmia, metabolic acidosis, rhabdomyolysis, acute renal failure, hyperlipidemia, and enlarged or fatty liver. Mannitol is a hyperosmolar agent routinely employed to treat increased intracranial pressure (ICP) by drawing water from intracellular into extracellular compartments along osmotic gradients. One study showed that an accumulative dose of mannitol is an independent risk factor of AKI following cerebral trauma.19 In patients with normal kidney function, a total mannitol dose of more than 1100 g may contribute to AKI, whereas only a lower dose of 300 g may promote AKI in patients with preexisting kidney disease. Risk factors associated with developing AKI in NICU patients receiving mannitol are congestive heart failure and a high APACHE II score.20 The mechanism of mannitol-induced kidney injury is unclear. Renal vasoconstriction and tubular vacuolization are believed to play a crucial role. Hypertonic saline is increasingly utilized to treat cerebral edema especially when mannitol is ineffective or contraindicated (eg, anuric renal failure). The problem of hypertonic saline is hyperchloremia potentially contributing to AKI. A study of SAH patients reported that the likelihood of developing AKI increases 5.4% for every 1 mEq/L increase in serum sodium.21 Mechanisms of AKI are demonstrated in Table 23.2.
Paper 2 Answers
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal in Get Through, 2014
Propofol is not safe for use in high-dose prolonged infusions due to the risk of propofol infusion syndrome. This is a syndrome of metabolic acidosis, rhabdomyolysis, hepatomegaly, hypertriglyceridaemia, renal and hepatic failure and is often fatal. Risk factors include high dose infusion over long periods (>4 mg·kg−1·hr−1 for more than 24 hours) and glucocorticoid use.
GABA(A) receptor-targeted drug development -New perspectives in perioperative anesthesia
Published in Expert Opinion on Drug Discovery, 2019
Bernd Antkowiak, Gerhard Rammes
Propofol is the most frequently administered agent for induction and maintenance of sedation and anesthesia [7]. It was discovered in 1977 and approved by the Food and Drug Administration for usage in the United States in 1989 [9]. Propofol is on the World Health Organization’s List of Essential Medicines since 2016. The drug binds to more than two allosteric sites on αβγ-GABAA receptors [21,22]. A knock-in mutation in the β3-subunit largely reduced the hypnotic action of the drug in mice, providing evidence that GABAA receptors are the most important molecular targets for propofol [23]. Propofol is a fat-soluble drug that is highly bound to serum albumin. In humans the percentage of unbound propofol is only 0.98%[24]. The free concentration of propofol to cause anesthesia was estimated to be about 1.2 μmol/L [25]. Its use is associated with several adverse effects. Due to its hydrophobic nature, propofol is solubilized in lipid solutions. If vials are open and exposed to the air, the risk of bacterial contamination is high [26]. Propofol commonly causes pain upon injection [27] and dose-dependent cardiovascular [28] and respiratory depression [29]. Further disadvantages include emulsion instability [30] and hyperlipidemia [31]. Administration for prolonged sedation in the intensive care unit can lead to the development of the propofol-infusion syndrome, a serious complication characterized by acute refractory bradycardia [32].
The role of the clinical laboratory in diagnosing acid–base disorders
Published in Critical Reviews in Clinical Laboratory Sciences, 2019
Typical symptoms of propofol infusion syndrome are metabolic acidosis, dysrhythmias, rhabdomyolysis, and lipemic plasma. Propofol is a short-acting intravenously administered anesthetic agent widely used for sedation or anesthesia. Propofol may cause a high osmolal and high AG metabolic acidosis in rare cases when a high dose (>4 mg/kg/h) is used over a longer period of time. The urine color may become white [190], pink [191], or green [192].
Gamma-hydroxybutyrate: is it a feasible alternative to midazolam in long-term mechanically ventilated children?
Published in Current Medical Research and Opinion, 2019
Jörg Michel, Michael Hofbeck, Timo Merz, Matthias Kumpf, Anna Meiers, Felix Neunhoeffer
In our department we tried to counteract midazolam’s ceiling effect by administering GHB instead of midazolam for at least two days. We believed that a switch from midazolam to a different sedative agent is superior to adding another sedative agent to existing therapy. The latter strategy might result in a vicious circle where higher and higher doses of sedative agents are required when the receptors are saturated. Also, intensivists must focus on optimal dosing of the drugs, which might get neglected when too many analgesic and sedative agents are in use19,20. We chose the duration of two days for pausing midazolam because the elimination half-life of midazolam varies in critically ill patients and may be prolonged up to 36 hours21,22. With the pause of midazolam, we intended to free the GABAA receptors in order to require lower doses of midazolam when switching back from GHB. In contrast to other hypnotic or sedative agents, GHB seemed to be a reasonable alternative to midazolam since severe adverse events are not reported. GHB does not negatively impact arterial blood pressure18,23. It is reported that the high sodium content of the GHB infusion may increase serum sodium levels which might be a problem in neonates and infants18. However, this issue is negligible in a PICU setting where serum electrolytes are regularly tested. Also, we did not observe hypernatremia in our cohort. Most other alternatives to midazolam come with disadvantages. Propofol, which is known to be a short-acting and effective hypnotic agent, comes with the risk of the life-threatening propofol infusion syndrome and its use for sedation of children <16 years in PICU setting is prohibited in many countries24. Data about dexmedetomidine for its use in invasively ventilated pediatric patients are still poor and show no superiority over other sedative agents25–27. Also, since the patients of our cohort already received the alpha-2-agonist clonidine, a change from midazolam to dexmedetomidine did not seem to be promising. Other enteral sedative agents like chloral hydrate, melatonin or H1 antihistamines including hydroxyzine seem not to be powerful alternatives to maintain sufficient sedation in critically ill patients28. Also, as critically ill patients may suffer enteral malabsorption, the bioavailability of enteral administered medication is uncertain29. In our opinion, enteral sedative agents may therefore only serve as adjuvant agents. Sedation with inhalational anesthetics like sevoflurane is described as an alternative to the use of benzodiazepines but requires a special delivery system for PICU ventilators and overall experience outside of the operating room in PICUs is low30,31. In addition, there are data that inhalational anesthetics may be neurotoxic5,31–34.
Related Knowledge Centers
- Hyperkalemia
- Hypertriglyceridemia
- Kidney Failure
- Metabolic Acidosis
- Syndrome
- Rhabdomyolysis
- Heart Failure
- Anesthetic
- Sedative
- Propofol