Propofol is an intravenous agent used commonly for the induction and maintenance of anesthesia, procedural, and critical care sedation in children. The mechanisms of action on the central nervous system involve interactions at various neurotransmitter receptors, especially the gamma-aminobutyric acid A receptor. Approved for use in the USA by the Food and Drug Administration in 1989, its use for induction of anesthesia in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly as children are not “little adults”, in this review, we emphasize
 the maturational aspects of propofol pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exists despite the Food and Drug Administration mandating addition of antimicrobial preservative, calling for manufacturers’ directions to discard open vials after 6 h. While propofol has advantages over inhalation anesthesia such as less postoperative nausea and emergence delirium in children, pain on injection remains a problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening complication of propofol. At the time of this review, there is no direct evidence in humans for propofol-induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by propofol persist and continue to be a focus of research.

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Propofol: a review of its role in pediatric anesthesia and sedation

Impact of Acute Pain and Its Management for Thoracic Surgical Patients

Background: Little is known about age and cerebral autoregulation in children with traumatic brain injury (TBI). The authors compared cerebral autoregulation between young (aged <4 yr) and older (aged ≥4 yr) children with TBI. Methods: After University of Washington's institutional review board approval, a retrospective analysis of prospectively collected data (May 2002 and June 2007) was performed. Eligibility criteria included age 16 yr or younger, moderate to severe (admission Glasgow Coma Scale score <13) TBI, TBI on computed tomography scan, and tracheal intubation. Cerebral autoregulation testing was performed within 72 h after TBI, and autoregulation was quantified using the autoregulatory index. An autoregulatory index less than 0.4 represents impaired cerebral autoregulation. The 12-month Glasgow outcome score was measured. Data are presented as mean ± SD or range. Results: Thirty-seven children (8.9 ± 5.1 yr; 0.8-16 yr) were enrolled. Children younger than 4 yr had a higher incidence of impaired cerebral autoregulation (8 of 10 vs. 7 of 27; P = 0.006) and worse 12-month outcome (Glasgow outcome score 3.0 ±1.0 vs. 4.0 ± 1.0; P = 0.02) than older children. Age less than 4 yr (adjusted odds ratio, 12.2; 95% confidence interval, 1.5-98.5) and low Glasgow Coma Scale score (adjusted odds ratio for higher Glasgow Coma Scale, 0.53; 95% confidence interval, 0.30-0.96) were independently associated with impaired cerebral autoregulation. Conclusions: Age less than 4 yr was a risk factor for impaired cerebral autoregulation, independent of TBI severity. Age-related factors may play a role in the mechanisms maintaining or worsening cerebral autoregulation in children after TBI.

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Young age as a risk factor for impaired cerebral autoregulation after moderate to severe pediatric traumatic brain injury.

NSAIDs inhibit the cyclo-oxygenase enzymes, and decrease peripheral and central prostaglandin production. In addition to reducing the inflammation that accompanies tissue injury, decreasing prostaglandin production attenuates the response of the peripheral and central components of the nervous system to noxious stimuli. Such a reduction in the response to pain can reduce the peripheral and central sensitisation induced by noxious stimuli, and reduce the pain experienced in response to subsequent noxious stimuli. These properties would seem to make NSAIDs ideal drugs to use in a pre-emptive fashion, where analgesics are administered prior to a noxious stimulus, such as surgery, with the expectation that reduction in peripheral and central sensitisation will lead to a decrease of pain. However, the available perioperative trials of pre-emptive NSAID use have yielded modest or equivocal results, and these may be due, in part, to controversy associated with the definition of pre-emptive analgesia and how to conduct the corresponding clinical trials. Although NSAIDs may have a limited ability by themselves to induce a pre-emptive analgesic effect, the available trials suggest how the perioperative use of these drugs may be made more effective. It is expected that NSAIDs will play an increasing role in multimodal analgesia and pain relief in general.

What is the Role of NSAIDs in Pre-emptive Analgesia?

OBJECTIVE: Although volatile anesthetics have been widely accepted in anesthetic management for neurosurgery, they reduce vascular resistance, resulting in increased cerebral blood flow and increased intracranial pressure (ICP). In patients with elevated ICP who undergo craniotomy, the increase in ICP during surgery from inhaled anesthetics can make the surgery more difficult, thereby increasing the risk of ischemic cerebral insults. Total intravenous anesthesia (TIVA) using propofol and analgesic drugs (remifentanil or fentanyl) and excluding simultaneous administration of any inhaled drugs is being used in patients undergoing craniotomy because of its potential to reduce ICP and ease access to the operative site. METHODS: We reviewed the literature and describe our experience with TIVA, with emphasis on hemodynamic stability, effects on ICP, emergence from anesthesia, extubation times, and return of cognitive function in patients undergoing craniotomy for space-occupying lesions. RESULTS: TIVA with propofol is similar to inhaled anesthetics with regard to hemodynamic stability, emergence times, extubation times, early cognitive function, and adverse events. In several prospective, randomized clinical trials, evidence suggests that ICP is decreased and cerebral perfusion pressure is increased in patients receiving TIVA when compared with those receiving volatile anesthetics during elective craniotomy procedures. CONCLUSION: The impact of TIVA on ICP, brain swelling, and access to the operative site in patients with severely elevated ICP has yet to be evaluated and is the subject of a future study at our institution.

Total intravenous anesthesia: advantages for intracranial surgery.

Purpose
Propofol, by virtue of its favourable pharmacokinetic profile, is suitable for maintenance of anesthesia by continuous infusion during neurosurgical procedures in adults. It is gaining popularity for use in pediatric patients. To determine the effects of propofol on cerebral blood flow in children, middle cerebral artery blood flow velocity (Vmca) was measured at different levels of propofol administration by transcranial Doppler (TCD) sonography.

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Propofol decreases cerebral blood flow velocity in anesthetized children.

https://www.anesthesiology.theclinics.com/article/S0889-8537(03)00055-5/pdf

Novel concepts for analgesia in pediatric surgical patients

CLINICAL QUESTIONS What is the role of plasma exchange and what is the optimal dose of glucocorticoids in the first 6 months oftherapyofpatientswithantineutrophilcytoplasmicantibody(ANCA)-associatedvasculitis(AAV)?This guideline was triggered by the publication of a new randomised controlled trial. Existing guideline recommendations vary regarding the use of plasma exchange in AAV and lack explicit recommendations regarding the tapering regimen of glucocorticoids during induction therapy. The guideline panel makes a weak recommendation against plasma exchange in patients with low or low-moderate risk of developing end stage kidney disease (ESKD), and a weak recommendation in favour of plasma exchange in patients with moderate-high or high risk of developing ESKD. For patients with pulmonary haemorrhage without renal involvement, the panel suggests not using plasma exchange (weak recommendation). The panel made

Mark W Farrar

Papers

Propofol decreases cerebral blood flow velocity in anesthetized children.

Novel concepts for analgesia in pediatric surgical patients

RAPID RECOMMENDATIONS Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis: a clinical practice guideline