Adjunts to Anesthesia

Adjuncts to Anesthesia

• Diphenhydramine competitively blocks H₁ receptors, has antimuscarinic and antiserotonergic activity.
• H₂ blockers decrease perioperative risk of aspiration pneumonia by decreasing gastric fluid volume and raising pH.
• Metoclopramide increases lower esophageal sphincter tone, speeds gastric emptying, and lowers gastric fluid volume.
• Ondansetron, granisetron, tropisetron, and dolasetron block serotonin 5-HT3 receptors, with minimal effect on dopamine receptors.
• Ketorolac is a nonsteroidal anti-inflammatory drug that inhibits prostaglandin synthesis, providing analgesia.
• Clonidine is an antihypertensive agent used in anesthesia for epidural, caudal, and peripheral nerve block, and pain management.
• Dexmedetomidine is a selective a₂-agonist with sedative properties.
• Doxapram stimulates carotid chemoreceptors stimulating hypoxic drive, increasing tidal volume.
• Naloxone reverses opioid agonist activity.
• Flumazenil reverses benzodiazepine sedation.
• Aspiration of gastric contents is a rare, potentially fatal event in anesthesia. Factors increasing the risk include full stomach, intestinal obstruction, hiatal hernia, obesity, pregnancy.
• Many drugs are used perioperatively to protect against aspiration, nausea, vomiting, or respiratory depression.

Aspiration

• Aspiration of gastric contents can complicate anesthesia, often resulting in aspiration pneumonia.
• Risk factors include a "full" stomach, intestinal obstruction, hiatal hernia, obesity, pregnancy, and inadequate anesthesia depth.
• Many approaches aim to reduce the risk, such as Sellick maneuver, rapid sequence induction.
• Anesthetized patients are at risk of passive aspiration due to reduced lower esophageal sphincter tone and gag reflex suppression.

Histamine-Receptor Antagonists

• Histamine is found in the central nervous system, gastric mucosa and other peripheral tissues.
• It is synthesized from the amino acid histidine.
• Histamine plays a role in HCl acid secretion in the stomach
• Histamine release can be stimulated by chemical, mechanical or immunological stimulation.
• H₁ receptors activate phospholipase C, while H₂ receptors increase intracellular cyclic adenosine monophosphate.
• H₃ receptors are primarily located on histamine-secreting cells and mediate negative feedback.
• H₁-receptor antagonists, including diphenhydramine, have multiple therapeutic uses, including allergic reactions, upper respiratory tract infections, vertigo, nausea, sedation, cough suppression, and dyskinesias..

H₂-Receptor Antagonists

• H₂-receptors, found in parietal cells, increase gastric acid secretion.
• H₂-receptor antagonists inhibit histamine binding to H₂ receptors, reducing gastric acid output.
• Cimetidine, famotidine, nizatidine, and ranitidine are H₂-receptor antagonists.
• These agents are used to treat peptic ulcers, hypersecretory states, gastroesophageal reflux disease (GERD), and prevent aspiration pneumonia perioperatively.

Proton Pump Inhibitors

• PPIs inhibit the proton pump of parietal cells, decreasing gastric hydrogen ion secretion.
• Omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole are examples.
• PPIs are used for peptic ulcer disease, GERD, and Zollinger-Ellison syndrome.
• Potential side effects include hepatotoxicity, interstitial nephritis, and interactions with other drugs.

Post Operative Nausea & Vomiting (PONV)

• PONV occurs in approximately 30-80% of patients.
• Risk factors include female gender, history of PONV/motion sickness, nonsmoker, use of opioids and duration of surgery
• Risk factors for children include age, surgery > 30 minutes, and history of PONV.
• Prophylactic antiemetics, including 5-HT3 antagonists, butyrophenones (dexamethasone), NK1-receptor antagonists, antihistamines and scopolamine are used.

Butyrophenones

• Droperidol is a butyrophenone used for PONV prophylaxis.
• This drug is no longer commonly used due to concerns about QT prolongation, Torsades de Pointes, and cardiac effects.
• Other phenothiazines, such as promethazine, may be alternative options, however, are not commonly used for prophylaxis of PONV.

Doxapram

• Doxapram is a peripheral and central nervous system stimulant
• It selectively activates carotid chemoreceptors.
• It is not a reversal agent and thus should not replace standard supportive therapies.
• Stimulation leads to an increase in tidal volume and respiratory rate.
• The drug should not be used in patients with underlying conditions such as epilepsy, cerebrovascular disease, acute head injury, or bronchial asthma.

Naloxone

• Naloxone is a competitive opioid receptor antagonist with high affinity for µ receptors.
• It reverses the effects of opioid-induced respiratory depression.
• It is used in emergency situations involving overdose or opioid-related respiratory issues.
• Rapid reversal can lead to a surge in sympathetic activity.

Flumazenil

• Flumazenil is a benzodiazepine receptor antagonist.
• It reverses benzodiazepine-induced sedation and overdose.
• It should be used cautiously, especially in patients with pre-existing conditions, including head injuries.

Dexamethasone

• Dexamethasone is a synthetic corticosteroid that reduces the incidence of PONV.
• Its mechanism of action is not fully understood, but it may have analgesic and mild euphoric effects.
• It may increase postoperative blood glucose.
• It should be administered at induction, not at the end of surgery.

Neurokinin-1 Receptor Antagonists

• Aprepitant is a neurokinin-1 receptor antagonist that reduces PONV.
• It's often used in combination with other agents given its additive effect.

Ketorolac

• Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID).
• Decreases postoperative need for opioid analgesics as it inhibits prostaglandin synthesis.
• It has minimal central nervous system side effects and is commonly used post-operatively.

Clonidine

• Clonidine is an imidazoline derivative with prominent α2-adrenergic agonist activity.
• It reduces sympathetic tone by decreasing systemic vascular resistance, heart rate, and blood pressure.
• It has analgesic effects, especially during epidural/caudal/peripheral nerve blocks, thus decreasing the need for opioids.
• It is also indicated in chronic neuropathic pain management.

Dexmedetomidine

• Dexmedetomidine is a selective α2-agonist with sedative properties.
• It causes dose-dependent sedation, anxiolysis, analgesia, and blunting of sympathetic responses.
• It spares opioids and is particularly useful in mechanically ventilated patients.
• Side effects include bradycardia, heart block, and hypotension.