Medication Review

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Class: Isopropylphenol 

MOA: GABA-A receptor agonist.  GABA is an inhibitory neurotransmitter causing sedation. Propofol potentiating the GABA receptor, increasing the conduction of chloride into the neuron and hyperpolarizing the cell.

Onset: immediate Duration: 5-20 mins due to rapid redistribution. Half-life 0.5-1.5 hours 

Metabolized by lung and liver. Excreted by kidneys.

Contraindications: Though rare, sodium meta-bisulfate used in generic formulations can precipitate an asthma attack. Egg allergy is not supported in literature as a contraindication as propofol is made from egg lecithin (the yolk) and egg allergies are to albumin in egg whites. 

Considerations for bariatric patients:  Propofol induction doses should be based on lean body weight (ideal body weight x 1.3) and infusions based on total body weight. Propofol does not accumulate in morbidly obese patients. While it's volume of distribution is increased in obese patients, it does not do so proportionally with fat mass, as fat tissue is not perfused well as lean mass. Propofol has antiemetic properties partially related to inhibition of serotonin receptors. 

Class: Imidizole derivitive

MOA: Alpha-2 agonist. Its sedative effect comes from acting on post-synaptic alpha-2 receptors in the locus corelous of the pons.  It's mild analgesic effects are thought to be mediated by α-2 receptor binding in the dorsal horn of spinal cord and the subsequent reduction in substance P and glutamate which are responsible for nociceptive transmission.

 It has a biphasic effect on the cardiovascular system. Initial high plasma concentrations after a bolus cause a transient increase in SVR (and bradycardia from the baroreceptor reflex). As plasma concentration lowers, sympatholysis and vasodilation occur from stimulation of alpha 2 receptors in vascular endothelium. This results in hypotension with a MAP drop of 13-27% from baseline. Hemodynamic effects from boluses can be minimized by decreasing the dose or increasing the time the bolus is infused (20 mins instead of 10). Predictors for problematic hypotension include age over 65, history of CAD, and lower baseline MAPs. Reduces shivering postop.

Onset: 5 minutes, peak effect 15 mins. Duration: elimination half life 2 hours  Metabolism: liver. Excreted by kidneys and GI tract

Contraindications: Minimal. Careful in patients that will not tolerate bradycardia and/or hypotension

Considerations for bariatric cases:  There is little literature on how to dose dexmedetomidine in obese patients, but in small, controlled studies, it appears it should be dosed based off IBW or LBW, but not total body weight as it is in non-obese adults. Multiple studies have shown a decrease in opioid use when dexmedetomidine has been incorporated into anesthetic regimens for bariatric surgical cases.

Class: Phencyclidine derivative. Synthetic PCP with less psychotropic effects.

MOA: NMDA receptor antagonist.  Inhibits glutamine, the excitatory neurotransmitter of the CNS, causing dissociation between thalamus and limbic system.  Increases HR, cardiac output, SNS tone, and PVR. Good bronchodilator. While is a moderately emetic drug, its use in a multi-modal anesthetic decreases the need for opioids which would otherwise greatly increase the risk of PONV. Analgesic effects come from binding to mu receptors. Relives somatic pain better than visceral pain. Blocks central sensitization and wind-up in dorsal horn of spinal cord. 

 Onset: 30 seconds. Duration: 5-15 mins. Metabolism: Liver into metabolite norketamine (1/3 as potent). Excreted by kidneys. Not effected by liver or kidney insufficiency.

Contraindications: seizures, patients with psychiatric disorders who may be at risk of harm from emergence delirium (midazolam can help prevent this).  Be aware that ketamine can falsely increase BIS monitoring.

Considerations for bariatric patients: Dose based on ideal body weight. Multiple studies looking at the impact of ketamine in bariatric surgery have found that although opioid consumption and PONV rates were not changed over a 48-hour period, there was significant improvement in pain scores, opioid requirements, and rates of PONV in the immediate post op period (24 hours).

Acetaminophen

Non-steroidal analgesic. Does not have anti-inflammatory effects but classified as an NSAID because it inhibits COX enzymes. Multiple studies have shown that preoperative PO acetaminophen is no less effective at decreasing post operative pain when compared to intravenous route. Dosing is the same (15mg/kg). Contraindications include severe hepatic impairment. 

Dexamethasone

 Glucocorticoid. Although the MOA is not known, likely exhibits anti-emetic properties via direct central action at the solitary tract nucleus, interaction with the serotonin and the NK1 and NK2 receptors, and regulation of the hypothalamic-pituitary-adrenal axis. Dosing is not standardized, but 0.25mg/kg up to 10mg is an accepted dose in literature for anti-emetic purposes.

Ondansetron

Serotonin receptor antagonist.   Literature says that when performing prolonged surgical procedures, late administration of ondansetron (within 30 minutes prior to completing the surgery) is significantly more effective in the prevention of late PONV than when administered prior to the induction of anesthesia. Contraindicated with prolonged QT interval.

Scopolamine

Anticholinergic. Crosses the blood brain barrier and is the strongest anticholinergic used in anesthesia, which is why it is given transdermally. Blocks the action of acetylcholine producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. It is structurally very similar to atropine. Place at least two hours before surgery ideally. Peaks in 24 hours and lasts 72 hours. May cause pupil dilation, blurry vision, dryness of the mouth. Contraindicated in narrow-angle glaucoma and belladonna allergies.  

Haldol

Butyrophenone derivative/anti-dopaminergic. Use as an anti-emetic is off label. The best time to give in the perioperative period is not well established, but 1 mg given in PACU is shown to be as effective as Ondansetron in the literature. Relative risks of sedation are decreased when doses are limited to 1 mg. Contraindications include QT prolongation and Parkinsons. 

Promethazine

Antihistamine and anti-dopaminergic anti-muscarinic. Literature suggests a decreased dose of 6.25 mg can be given for similar PONV reduction and less sedative effects.  Caution in Parkinsons and prostate hypertrophy. Vesicant; please dilute.