Post-Operative Nausea and Vomiting
Note: much of the following is a summary of the IARS consensus guidelines for PONV [Gan TJ et. al. Anesth Analg 97: 62, 2003; FREE Full-text at Anesthesia & Analgesia] and the society for Ambulatory Anesthesia Guidelines for PONV [Gan et. al. Ambulatory Anesthesiology 105: 1615, 2007]
Incidence and Risk Factors
PONV is the leading cause of unanticipated hospital admission. Among high risk patients, the incidence can be as high as 80% [Apfel et. al. Anesthesiology 91: 693, 1999], however according to the IARS guidelines, prophylactic treatment of all patients is not cost-effective, and the panel agreed that not all patients should receive prophylaxis, but rather, only those who are at “moderate” risk [Gan TJ et. al. Anesth Analg 97: 62, 2003]; FREE Full-text at Anesthesia & Analgesia. Unfortunately, the committee did not define “moderate” risk – “the decision was made, instead, to allow the health care professionals who use the guidelines to determine the level of risk according to their own local and institutional norms”
Apfel has defined a simple, reliable metric for assessing PONV risk based on analysis of 2700 patients at two centers – the four major risk factors are female gender, non-smoker, history of PONV (or car sickness), and opiate use. The incidence of PONV for 0, 1, 2, 3, or 4 risk factors is 10%, 20%, 40%, 60%, or 80%, respectively [Apfel et. al. Anesthesiology 91: 693, 1999]. Additionally, Apfel did not find an association between type of surgery and PONV. For children, the risks are the same, except that risk increases with age (until puberty).
Friedberg BL: Propofol-ketamine technique, dissociative anesthesia for office surgery: a five-year review of 1,264 cases. Aesthetic Plastic Surgery 23:70-74, 1999.
Potentially effective management changes include regional anesthesia (GA has an 11-fold increased risk), use of propofol, the use of supplemental oxygen for 2h after surgery [data from 231 randomized colon resection patients showed a nearly 2-fold reduction in PONV, Greif et. al. Anesthesiology 91: 1246, 1999, however systematic reviews of all the data on oxygen and vomiting suggest that, at best, it delays PONV, but does not prevent it], hydration [Yogendran Set. al. Anesth Analg 80: 682, 1995], and using < 2.5 mg neostigmine [Tramer et. al. Br J Anaesth 82: 379, 1999]. If a patient does experience PONV, the breakthrough treatment should be of a different class than the prophylaxis.
Ondansetron 4 mg (NNT = 7, NNH = 36 for HA, 31 for elevated LFTs, 23 for constipation, $13.22/vial at the University of Virginia) is most effective when used at the end of the case. Dexamethasone 8-10 mg (NNT 4, 2.5-5 mg are just as effective [Liu K et. al. Anesth Analg 89: 1316, 1999 FREE Full-text at Anesthesia & Analgesia; Wang JJ et. al. Anesth Analg 91: 1404, 2000 FREE Full-text at Anesthesia & Analgesia], furthermore there are no reports of adverse effects with one bolus administration). Droperidol 0.625-1.25 mg (NNT = 5) is most effective at the end of surgery, and is particularly effective when administered in patients using a morphine PCA (NNT = 3), however a FDA black box warning  has curtailed enthusiasm.
FDA Warning re: Droperidol
This warning is based on 10 reported cases from 1997-2002 [Habib AS et. al. Anesth Analg 96: 1377, 2003 FREE Full-text at Anesthesia & Analgesia] – these 10 cases were all with 1.25 mg or less, but in none of them could a definitive cause-effect relationship be described, and in five of them there were substantial confounding factors. Assuming that droperidol sales averaged 11 MM ampules per year, and that these events were truly related to droperidol, the authors estimated that the incidence of associated events was 1:150,000. If not for the black box warning, the committee would have made this the first choice.
The Guidelines state that only moderate/high risk patients should receive PONV prophylaxis, and that these patients should receive combination therapy. Interesting, the ambulatory surgery Guidelines suggest haldol, which at 0.5-2 mg IM or IV has been shown on meta-analysis to reduce PONV with a NNT of 4-6 [Buttner et. al. Anesthesiology 101: 1454, 2004], however it does cause QTc prolongation as well
Medications with No Reliable Effect
Note that metocopramide, ginger, and cannabanoids have no effect
Incidence and Genetics
Incidence is 1:10,000 general anesthetics. Unexpected rise in ETCO2 is the most sensitive and specific sign of MH. Masseter muscle rigidity is more common in children than in adults, leads to MH in ~ 25% of cases, and is associated with myoglobinuria. Trigger agents for MH include all volatile anesthetics (not including nitrous oxide) and succinylcholine. Predisposing disorders include central core disease and rare myotonias (ex. hypokalemic periodic paralysis).
Note that it is very difficult to accurately test for and characterize this disease. Susceptible patients may receive general anesthesia with no complications, and subsequently trigger MH. In fact, MH may only be expressed in 34 to 54% of occurrences according to the Danish MH Registry. Furthermore, there are case reports of patients receiving up to 13 general anesthetics prior to developing MH.
MH is inherited in an autosomal dominant fashion, with variable penetrance.
The halothane-caffeine contracture test is the gold standard. The North American test has a 100% sensitivity and a 78% specificity (requires a positive response in only one of the two tests), while the European test has a 98% sensitivity and a 93% specificity (requires a positive response in both tests). There is also a clinical grading scale which examines muscle rigidity, myonecrosis, respiratory acidosis, temperature, and cardiac involvement to give a likelihood scale.
Treatment 1. Discontinue all triggering agents 2. Hyperventilate with 100% O2 @ 10L/min 3. Dantrolene 2.5 mg/kg, prn, for at least 36 hours. GET ASSISTANCE WITH MIXING (20 mg vials in 50 cc of sterile distilled water, preferably at 40C). Note that each 20 mg dantrolene contains 300 mg of mannitol, thus a foley catheter must also be inserted. Titrate dantrolene (and bicarbonate) to heart rate, temperature, and PaCO2. 4. Cool by all routes available (esp. nasogastric lavage, also ice packs) 5. Treat hyperkalemia (calcium chloride, glucose, insulin, bicarbonate, hyperventilation). Do not give potassium if hypokalemia results, however, as it may retrigger MH 6. Beware dysrhythmias, but do not treat with CCB (lidocaine is safe) 7. Central mixed venous or femoral venous blood gases are superior to ABGs as a guideline for therapy 8. Send creatinine, coags, CK
Note that as many as 25% of patients may recrudesce. DIC is common, especially if temperature exceeds 41C. Myoglobinuric renal failure is also common. Severe pain and weakness are sequelae of MH, and muscle recovery can take months
Conditions which mimic MH: sepsis (most often confused with MH), pheochromocytoma, hypoxic encephalopathy, mitochondrial myopathies, periodic paralysis (hypokalemic and hyperkalemic varieties).
Anaphylaxis can be associated with cardiovascular collapse that is difficult to manage and does not respond to treatment with epinephrine. Because anaphylaxis is so uncommon, a randomized, controlled trial in humans is impossible to conduct. Epinephrine remains the treatment of choice. That said, Schummer et. al. reported six cases in which the use of vasopressin was successful in the treatment of anaphylactic shock refractory to epinephrine [Schummer C et. al. Anesth Analg 107: 620, 2008]; FREE Full-text at Anesthesia & Analgesia