HOSPITAL OF THE UNIVERSITY PENNSYLVANIA
Patrick Neligan, Sander Schlichter, Mary Tannouri, Kimberley Lee, Vonda Davidson, Christopher Ward, Carmella Shemansik
PONV is a multifactorial problem. Causes other than anesthesia should be considered. Hypotension and hypovolemia are major contributors to PONV and one must ensure that adequate fluid resuscitation has been achieved based on blood pressure measurements, heart rate, and urinary output. This is a particular problem in patients that have undergone neuraxial anesthesia (spinal or epidural) The majority of patients undergoing ambulatory surgery require at least 2ml/kg/hour fasting7 or 30ml/kg total intravenous fluid (in addition to replacement of blood losses).8
A stepwise pharmacologic approach is recommended. There are several classes of drugs used for both prophylaxis and treatment of PONV. These agents have differing affinities for different receptor sites, and can be used in combination. The anticholinergic agent scopolamine (hyoscine used transdermally) is used largely as a prophylactic agent and should be applied the evening before surgery or at least four hours before the end of the procedure to have efficacy. Common side effects include dry mouth, and visual disturbances.
The antihistamine class includes drugs such as promethazine (12.5-25mg IV), and diphenhydramine (25-50mg IV). The act on the chemoreceptor trigger These drugs also have significant anti-dopaminergic and anticholinergic effects, and are effective for mono-therapy of established PONV. Common side effects of these drugs include drowsiness, dizziness, and photosensitivity.
Metoclopramide is an antidopaminergic agent. The usual dose is 10mg IV and its major effect is by eliciting a prokinetic effect on the bowel. Significant controversy exists in regard to its efficacy in PONV. Approximately 50% of studies show that it is no more efficacious than placebo.
Dexamethasone (8-10mg IV), a corticosteroid, is effective as a prophylactic agent rather than rescue therapy. There are little to no side effects after being given a single dose. The mechanism of action of corticosteroids is unknown.
Ondansetron (Zofran 4-8mg IV) is a serotonin 5-HT3 receptor antagonist, a class of drugs that includes dolasetron (12.5mg IV), granisetron (0.35-1mg IV), and tropisetron (5mg IV). These agents act centrally and peripherally. They reduce vagal activity, thus reducing activity in the vomiting center, and block serotonin receptors in the chemoreceptor trigger zone. These drugs are most effective when given at the end of surgery. They are largely ineffective rescue drugs. They have a good side effect profile that includes headache, constipation, and transient elevation of liver function tests.
Droperidol is a butyrophenone and acts as an antagonist at the dopamine D2 receptor. The usual dosage is 0.625 – 1.25 mg intravenously. Recently an FDA black box warning was issued for this drug because of its increased risk of QT prolongation and/or torsade de pointes. This drug has been in use for approximately thirty years and the FDA warning is based on ten case reports over that period of time. FDA recommendations include reserving droperidol for use in patients who fail to respond to other adequate treatment modalities. If being used, the FDA recommends a 12 lead EKG prior to administration to evaluate for QT prolongation and subsequently monitoring EKG tracing for 2-3 hours after administration.
Clinical research has focused on preventative, rather than rescue, therapy. In general, it has been shown that if prophylaxis failed with one antiemetic, then rescue therapy should target a different receptor and hence a drug from another class of antiemetics. Habib and colleagues9 demonstrated that when ondansetron (4mg) was used as a prophylactic agent, repeat doses of ondansetron was inferior to doperidol, metoclopramide, promethazine, and dimenhydrinate in achieving complete response. However, promethazine was the only antiemetic that achieved statistical significance.9 When droperidol (0.625-1.25mg) was used for prophylaxis, the use of ondansetron, promethazine, and dimenhydrinate for rescue therapy was more effective at achieving a complete response than a repeat dose of droperidol, but statistical significance was achieved only with promethazine and dimenhydrinate. The same group retrospectively analysed data on three thousand sixty-two patients that received ondansetron and 752 received promethazine after failure of ondansetron prophylaxis. The complete response (no PONV and no further rescue) was 68% after administration of promethazine and 50% after ondansetron administration (P < 0.0001).10 There was no difference in complete response between 6.25 mg and higher doses of promethazine. This is consistent with earlier data on repeat dosing of ondansetron.11
1. Gold BS, Kitz DS, Lecky JH, Neuhaus JM: Unanticipated admission to the hospital following ambulatory surgery. JAMA: The Journal of the American Medical Association 1989; 262: 3008-10
2. Cohen MM, Duncan PG, DeBoer DP, Tweed WA: The postoperative interview: assessing risk factors for nausea and vomiting. Anesthesia Analgesia 1994; 78: 7-16
3. Gan T, Sloan F, Dear GL, El Moalem HE, Lubarsky DA: How much are patients willing to pay to avoid postoperative nausea and vomiting? Anesthesia Analgesia 2001; 92: 393-400
4. Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, Kovac A, Philip BK, Sessler DI, Temo J, Tramer MR, Watcha M: Consensus guidelines for managing postoperative nausea and vomiting. Anesth.Analg. 2003; 97: 62-71, table
5. Cook R, Anderson S, Riseborough M, Blogg CE: Intravenous fluid load and recovery. A double-blind comparison in gynaecological patients who had day-case laparoscopy. Anaesthesia 1990; 45: 826-30
6. Gan TJ, Glass PS, Howell ST, Canada AT, Grant AP, Ginsberg B: Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea. Anesthesiology 1997; 87: 779-84
7. Maharaj CH, Kallam SR, Malik A, Hassett P, Grady D, Laffey JG: Preoperative Intravenous Fluid Therapy Decreases Postoperative Nausea and Pain in High Risk Patients. Anesthesia Analgesia 2005; 100: 675-82
8. Magner JJ, McCaul C, Carton E, Gardiner J, Buggy D: Effect of intraoperative intravenous crystalloid infusion on postoperative nausea and vomiting after gynaecological laparoscopy: comparison of 30 and 10 ml kg(-1). Br.J.Anaesth. 2004; 93: 381-5
9. Habib AS, Gan TJ: The effectiveness of rescue antiemetics after failure of prophylaxis with ondansetron or droperidol: a preliminary report. J Clin Anesth 2005; 17: 62-5
10. Habib AS, Reuveni J, Taguchi A, White WD, Gan TJ: A comparison of ondansetron with promethazine for treating postoperative nausea and vomiting in patients who received prophylaxis with ondansetron: a retrospective database analysis. Anesthesia Analgesia 2007; 104: 548-51
11. Kovac AL, O'Connor TA, Pearman MH, Kekoler LJ, Edmondson D, Baughman VL, Angel JJ, Campbell C, Jense HG, Mingus M, Shahvari MB, Creed MR: Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial. J Clin.Anesth 1999; 11: 453-9