Nagelhout Exam 3

• Medical conditions that increase the risk of a prolonged QT syndrome include:
  • Congestive heart failure
  • Bradycardia
  • Hypertension
  • Heart block
  • Cardiac hypertrophy
  • Cardiomyopathy
  • Hypomagnesemia
  • Use of medications, diuretics, antihypertensives, antidepressants, and antiarrhythmics
• Palonosetron (Aloxi) is a second-generation serotonin antagonist with a long half-life of 44 hours, making it preferable for PDNV prevention
• All first-generation 5-HT3 antagonists can prolong the QTc interval, reason why IV dolasetron is no longer available
• Serotonin syndrome can occur with concurrent use of 5-HT3 receptor antagonists and other serotonergic drugs like SSRIs and SNRIs

Neurokinin 1 Receptor Antagonists

• Aprepitant (Emend), fosaprepitant (Emend), netupitant/palonosetron (Akynzeo), and rolapitant (Varubi) are substance P/neurokinin 1 (NK-1) receptor antagonists
• NK-1 receptors are in the nucleus of the solitary tract (NST), involved in the central regulation of visceral function
• NK-1 receptor antagonists suppress activity at the NST, where vagal afferents from the GI tract converge with inputs from areas that initiate emesis
• Aprepitant is FDA-approved for PONV, while netupitant/palonosetron and rolapitant have been approved for CINV
• Rolapitant has a half-life of 180 hours and its active metabolite has a half-life of 158 hours, marketed for delayed CINV but may also be effective for PDNV prevention

Butyrophenones

• Small doses of Droperidol (0.625 to 1.25 mg) prevent and treat PONV, administered at the end of surgery
• Droperidol acts as a dopamine receptor blocking agent in the CNS
• It may cause extrapyramidal side effects and is contraindicated in patients with Parkinson's disease
• In 2001, the FDA issued a black box warning restricting its use due to potential prolongation of the QT interval, suggesting an ECG be performed before use
• Haloperidol also has antiemetic properties when used in low doses of 1 to 2 mg, administration at the beginning or end of surgery is equally efficacious
• Haloperidol has similar effects to droperidol on the QT interval but lacks a black box warning, some clinicians use it as an alternative to droperidol

Transdermal Scopolamine

• The scopolamine patch is an effective antiemetic applied the evening before surgery
• It has an onset time of approximately 4 hours and a minimum duration of 24 hours
• It prevents nausea and vomiting by blocking transmission of cholinergic impulses from vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center
• Common side effects include sedation, blurred vision, dizziness, and dry mouth
• Most effective for preventing nausea with patient-controlled analgesia

Benzodiazepines

• Midazolam may have a clinically significant antiemetic effect, preoperative or intraoperative IV midazolam is associated with decreased PONV, nausea, vomiting, and rescue antiemetic
• Midazolam decreases dopamine's emetic effect in the chemoreceptor trigger zone and decreases serotonin release by binding to the GABA receptor complex
• Administering a sedative near the end of surgery may prolong recovery, limiting the dose

Metoclopramide

• A weak antiemetic, exerts a mild dopamine receptor blocking effect unless doses greater than 20 mg are used
• It has a short half-life of 30 to 45 minutes, reports note little effect if given at the beginning of surgery
• Dyskinesia or extrapyramidal effects can be seen with higher doses
• Like droperidol, it is contraindicated in patients with Parkinson's disease
• It has potent gastrokinetic effects, its use is also contraindicated for patients with intestinal obstructions

Clinical Use of Antiemetics

• Guides the use of antiemetics based on common risk factors
• Multimodal PONV and PDNV prophylaxis should be considered for patients at moderate to high risk for PONV
• Prophylaxis in children at moderate or high risk for PONV should include combination therapy using a 5-HT3 antagonist and a second drug
• The effects of interventions from different drug classes are additive, combining interventions has an additive effect in risk reduction
• When rescue therapy is required, the antiemetic should be chosen from a different therapeutic class than the drugs used for prophylaxis and potentially one with a different mode of administration
• If PONV occurs within 6 hours postoperatively, patients should not receive a repeat dose of the prophylactic antiemetic
• An emetic episode more than 6 hours postoperatively can be treated with any of the drugs used for prophylaxis except dexamethasone, transdermal scopolamine, aprepitant, and palonosetron
• Agents with a rapid onset are preferred

Psychiatric Drugs and Anesthesia

• The incidence of psychiatric illness is increasing, with an estimated 9.6 million individual adults (4.1% of adults in the United States)
• Anxiolytic medication (AXM) was used by 16% of patients undergoing a noncardiac operation, it was an independent risk factor for poorer short-term outcome after surgery
• Antidepressant medications were used by 21% of patients, but they were not an independent risk factor for poor outcome
• Maintaining antidepressants, anxiolytics, antipsychotics, will ensure the patient's disease is better controlled during surgery
• Modern anesthetic techniques can be adapted to the patient's condition and drug therapy

Antidepressants

• Depression is be treated with antidepressive medications, psychotherapy, electroconvulsive therapy (ECT), or a combination
• Antidepressant treatment is usually given for 6 to 9 months following remission to consolidate recovery, long-term maintenance therapy is indicated for recurrent depressive episodes

Select Serotonin Reuptake Inhibitors

• SSRIs are first-line therapy for major depression
• Common side effects include restlessness, insomnia, nausea, diarrhea, headache, dizziness, fatigue, and sexual dysfunction
• SSRIs can cause hyponatremia, particularly in elderly patients, and increase the risk of bleeding
• When SSRIs are stopped abruptly, discontinuation symptoms (including nervousness, anxiety, irritability, electric-shock sensations, bouts of crying, dizziness, insomnia, confusion, nausea, and vomiting) can occur
• SSRIs have an inhibitory effect on CYP450 isoenzymes and may interact with many other drugs that rely on hepatic metabolism
• Citalopram and escitalopram may prolong the QT interval
• Unless a patient-specific concern develops, the SSRI should be continued throughout the perioperative period

Serotonin Syndrome

• Caused by individual drugs, an overdose, or, most commonly, a drug interaction
• Thought to be overstimulation of 5-HT1A as a result of an excess of serotonin precursors or agonists, increased serotonin release, reduced serotonin uptake, and decreased serotonin metabolism
• Characterized by mental status changes, autonomic instability, neuromuscular hyperactivity, and hyperthermia
• May occur with minutes or up to 24 hours after medication use, dose change, or adding a serotonergic drug
• Diagnosis is made using the Hunter Serotonin Toxicity Criteria
• Most cases are treated by cessation of the drugs and supportive care
• First-line therapy includes cyproheptadine, an H₁-receptor antagonist

Tricyclic Antidepressants

• TCAs remain alternatives to the SSRIs and SNRIs for patients with moderate to severe treatment-resistant depression
• Cause anticholinergic effects (urinary retention, constipation, dry mouth, blurred vision, and confusion), orthostatic hypotension, weight gain, sedation, and sexual dysfunction
• Amitriptyline should be avoided in patients with a history of heart disease
• Patients treated with TCAs may have altered responses to anesthesia-related drugs
• Administer a direct-acting drug such as phenylephrine for hypotension

Monoamine Oxidase Inhibitors

• Used only when other first-line treatments are ineffective due to risk of drug and food interactions eliciting a hypertensive crisis, the risk of serotonin syndrome, and difficulty with proper dosing
• MAO-A preferentially metabolizes serotonin, norepinephrine, and epinephrine
• MAO-B preferentially metabolizes phenylethylamine
• Severe cases of serotonin syndrome have been reported in patients treated with MAOIs who took over-the-counter dextromethorphan, the illegal methylenedioxymethamphetamine (Ecstasy), or who started treatment with serotonin reuptake inhibitors, meperidine, or atypical antipsychotics
• The use of meperidine in a patient treated with MAOIs may result in agitation, headache, skeletal muscle rigidity, hyperpyrexia, and death
• In the past, these drugs were discontinued prior to surgery, however, the safest approach is to continue these drugs and adjust the anesthetic plan to avoid meperidine and indirect-acting vasopressors

Serotonin Norepinephrine Reuptake Inhibitors

• SNRIs are given for major depression, anxiety, and other mood disorders, as well as chronic neuropathic pain
• Effects are mediated via increases in levels of serotonin and norepinephrine in the brain
• Side effects are similar to SSRIs but may also include increased sweating, tachycardia, and urinary retention
• Severe discontinuation symptoms can occur when these drugs are stopped
• SNRIs can cause a dose-dependent increase in blood pressure

Lithium

• Several drugs are used for the treatment of bipolar disorder
• Common adverse effects include tremor, thirst, polyuria, edema, and weight gain
• Nephrogenic diabetes insipidus can occur, increases the risk of lithium toxicity and may be irreversible, also hypothyroidism can occur with long term lithium treatment
• Lithium may cause mild leukocytosis, induce or exacerbate psoriasis, and cause skin reactions
• Discontinuation of lithium has been also associated with suicide
• Lithium prolongs the duration of nondepolarizing neuromuscular agents, and reduces the MAC of the inhalation agents

Antipsychotics

• Patients with schizophrenia and other serious mental illnesses are at increased risk for perioperative complications such as confusion and ileus
• Patients with schizophrenia may have higher pain thresholds, higher rates of death, and greater postoperative complications
• The antipsychotics include two major classes: dopamine receptor antagonists and serotonin-dopamine antagonists
• Anesthesia management consists of avoiding hypotension during induction due to additive depression of the anesthetic drugs
• A baseline ECG to assess QT interval prolongation may be helpful