Major Anesthetics

Summary

drug class: Major Anesthetics

type of drug: Systemic anesthetic

used to treat: The function of major anesthetics is to render patients unconscious during surgery through systemic action, particularly on the central nervous system.

overview of interactions:
• herbal constituent affecting drug performance and toxicity: Capsicum (Cayenne)

• herb affecting drug performance and toxicity: Humulus lupulus (Hops)

• herbs affecting drug performance and toxicity: Hypericum perforatum(St. John's Wort) and Piper methysticum(Kava)

• herb affecting drug toxicity: Silybum marianum (Milk Thistle)

• herb affecting drug performance and toxicity: Valeriana officinalis (Valerian)

• herb affecting drug toxicity: Zingiber officinale (Ginger)

preoperative protocols:
Murphy discussed cases of patients who had been taking herbs prior to surgery and how this had influenced the course of events, particularly the postponing of the procedure. She emphasized the importance of the perioperative team members asking patients about their use of herbal remedies during assessments of medication use.
(Murphy JM. AORN J. 1999 Jan;69(1):173-5, 177-178, 180-183.)

McLeskey et al found that 170 of 979 (17.4%) of presurgical patients were taking herbal products. The median age of the herb users and non-users was 62 years. Of the patients taking medicinal herbs, 55% took only one product, 45% took multiple products. In decreasing order, the most commonly utilized herbs among this group were: Gingko biloba (32.4%), garlic (26.5%), ginger (26.5%), ginseng and St. John's Wort (14%). The most commonly used nutritional supplements were glucosamine (17%), chromium picolinate (17%) and chondroitin (12%).
(McLeskey CH, et al. Annual Meeting of American Society of Anesthesiologists. October 1999.)

John B. Neeld, Jr, MD, President of the American Society of Anesthesiologists, has suggested that patients should stop taking herbal medications at least 2 to 3 weeks before surgery. Neeld and others have specifically cautioned against feverfew (Tanacetum parthenium) as potentially affecting PT time and increasing risk of bleeding, and St. John's Wort (Hypericum perforatum) and Kava-kava (Piper methysticum) as potentially prolonging the sedative effect of anesthesia due to a presumed MAOI-like action.
(Voelker R. JAMA, 281(20).May 26, 1999.1882.)

Caution, objectivity and continued research are necessary to clarify these issues. However, as of yet, no conclusive clinical research using human subjects, published case reports, or substantive pharmacological analysis has confirmed these claims of adverse effects or interactions due to herbs. Further, in 1985 el-Ganzouri et al examined the question of whether pharmaceutical monoamine oxidase inhibitors should be discontinued preoperatively and found that no complications attributable to MAOIs were observed in the 14 patients undergoing elective surgical procedures that they studied. They concluded that discontinuing chronic MAOI therapy prior to anesthesia and surgery is not necessary. Presumably the same would hold true if Hypericum or other herbs were found to exercise significant MAOI-like activity.
(el-Ganzouri AR, et al. Anesth Analg. 1985 Jun;64(6):592-596.)

In their 1999 brochure entitled "What You Should Know About Your Patients' Use of Herbal Medicines" the American Society of Anesthesiologists concluded that "use of herbal medications is not necessarily a contraindication for anesthesia. ... Patients should tell their physicians and physicians should ask about all herbal, dietary or other over-the-counter preparations as well as prescription medicine that the patient is taking. "


Interactions

herbal constituent affecting drug performance and toxicity: Capsicum (Cayenne)

• mechanism: Possible potentiation of anesthetic by capsaicin.

• herbal concern: Usage of cayenne at therapeutic dosages warrants physician supervision pre-operatively and possible avoidance for two to four weeks before surgery.

herb affecting drug performance and toxicity: Humulus lupulus (Hops)

• mechanism: The CNS-depressant action of hops may potentiate anesthetics.

• herbal concern: Usage of hops warrants physician supervision pre-operatively and possible avoidance for two to four weeks before surgery.

herbs affecting drug performance and toxicity: Hypericum perforatum(St. John's Wort) and Piper methysticum(Kava)

• reports: St. John's Wort (Hypericum perforatum) and kava (Piper methysticum) have been reported to prolong the sedative effect of anesthesia, possibly due to a presumed MAOI-like action. While numerous anecdotal reports and hypotheses as to mechanisms of action have circulated, no clinical research, published case reports or substantive pharmacological analysis has confirmed these claims of adverse effects or interactions.
(Murphy JM. AORN J. 1999 Jan;69(1):173-5, 177-178, 180-183; McLeskey CH, et al. Annual Meeting of American Society of Anesthesiologists. October 1999; Voelker R. JAMA. 281(20).May 26, 1999.1882.)

• herbal concern: Numerous authorities have suggested that patients stop taking herbal medications at least two to three weeks before surgery. Until more conclusive research is available, individuals are advised to report any usage of herbs to their treating physician well in advance of any planned surgery and to stop taking any such herbs for at least three weeks prior to surgery unless specifically agreed upon with and supervised by the physician coordinating the surgery.

herb affecting drug toxicity: Silybum marianum (Milk Thistle)

• research: Preliminary research indicates that Silymarin, a combination of the active bioflavonoids in milk thistle, can protect the liver from the type of damage that can result from major anesthetics.
(Fintelmann V. Med Klin 1973;68:809-815.)

• nutritional support: Dosage in the range of 140 mg of extracts containing 70-80% silymarin are given three times per day a week before the surgery and immediately after for at least one week.

herb affecting drug performance and toxicity: Valeriana officinalis (Valerian)

• mechanism: The CNS-depressant action of Valerian may potentiate anesthetics.

• herbal concern: Usage of valerian warrants physician supervision pre-operatively and possible avoidance for two to four weeks before surgery.

herb affecting drug toxicity: Zingiber officinale (Ginger)

• research: Two studies found that powdered ginger root administered prior to surgery reduced subsequent nausea and vomiting as effectively as the anti-nausea drug metoclopramide. However, Arfeen et al concluded that ginger BP in doses of 0.5 or 1.0 gram with oral diazepam premedication, one hour prior to surgery was ineffective in reducing the incidence of postoperative nausea and vomiting.
(Phillips S, et al. Anaesthesia 1993;48:715-717; Bone ME, et al. Anaesthesia 1990;45:669-671; Arfeen Z, et al. Anaesth Intensive Care. 1995 Aug;23(4):449-452.)

• mechanism: Anti-nausea action.

• nutritional support: One gram of powdered ginger root in capsules one hour before surgery was used in one of the studies cited above.
(Phillips S, et al. Anaesthesia 1993;48:715-717.)

References

American Society of Anesthesiologists. What You Should Know About Your Patients' Use of Herbal Medicines. 1999. http://www.asahq.org/ProfInfo/herb/herbbro.html

Arfeen Z, Owen H, Plummer JL, Ilsley AH, Sorby-Adams RA, Doecke CJ. A double-blind randomized controlled trial of ginger for the prevention of postoperative nausea and vomiting. Anaesth Intensive Care. 1995 Aug;23(4):449-452.
Abstract: The efficacy of ginger for the prevention of postoperative nausea and vomiting was studied in a double-blind, randomized, controlled trial in 108 ASA 1 or 2 patients undergoing gynaecological laparoscopic surgery under general anaesthesia. Patients received oral placebo, ginger BP 0.5g or ginger BP 1.0g, all with oral diazepam premedication, one hour prior to surgery. Patients were assessed at three hours postoperatively. The incidence of nausea and vomiting increased slightly but nonsignificantly with increasing dose of ginger. The incidence of moderate or severe nausea was 22, 33 and 36%, while the incidence of vomiting was 17, 14 and 31% in groups receiving 0, 0.5 and 1.0g ginger, respectively (odds ratio per 0.5g ginger 1.39 for nausea and 1.55 for vomiting). These results were essentially unchanged when adjustment was made for concomitant risk factors. We conclude that ginger BP in doses of 0.5 or 1.0 gram is ineffective in reducing the incidence of postoperative nausea and vomiting.

Bone ME, Wilkinson DJ, Young JR. et al. Ginger root - a new antiemetic: The effect of ginger root on postoperative nausea and vomiting after major gynaecological surgery. Anaesthesia 1990 Aug;45(8):669-671.
Abstract: The effectiveness of ginger (Zingiber officinale) as an antiemetic agent was compared with placebo and metoclopramide in 60 women who had major gynaecological surgery in a double-blind, randomised study. There were statistically significantly fewer recorded incidences of nausea in the group that received ginger root compared with placebo (p less than 0.05). The number of incidences of nausea in the groups that received either ginger root or metoclopramide were similar. The administration of antiemetic after operation was significantly greater in the placebo group compared to the other two groups (p less than 0.05).

Burnham BE. Garlic as a possible risk for postoperative bleeding. Plast-Reconst-Surg 1995;95:213.

D'Arcy PF. Adverse reactions and interactions with herbal medicines, part 1, adverse reactions. Adverse Drug Reactions and Toxicological Review 10 (Winter 1991) 189-208.

el-Ganzouri AR, Ivankovich AD, Braverman B, McCarthy R. Monoamine oxidase inhibitors: should they be discontinued preoperatively? Anesth Analg. 1985 Jun;64(6):592-596.
Abstract: Adverse cardiovascular responses to anesthesia during either electroconvulsive therapy (ECT) or elective surgical procedures were evaluated in 27 patients maintained on chronic (3 months-3 yr) monoamine oxidase inhibitor (MAOI) therapy. Changes in blood pressure and heart rate in study patients (n = 22 ECTs in 13 patients) undergoing ECT were not significantly different from those observed in patients having ECT without prior treatment with MAOIs (n = 45 ECTs in 45 patients). In both groups, blood pressure and heart rate increased significantly after ECT, but returned to baseline levels within 15 min. No complications attributable to MAOIs were observed in study patients (n = 14) undergoing elective surgical procedures. We conclude that discontinuing chronic MAOI therapy prior to anesthesia and surgery is not necessary.

Fintelmann V. [Postoperative behavior of serum cholinesterase and other liver enzymes.] Med Klin 1973 Jun 15;68(24):809-815. [Article in German]

Gadkari JV, Joshi VD. Effect of ingestion of raw garlic on serum cholesterol level, clotting time and fibrinolytic activity in normal subjects. J Postgrad Med 1991;37:128-131.

Gillis CN. Medicinal plants rediscovered. Seminars in Anesthesia, Perioperative Medicine and Pain. 1998; 17(4):319-330.

Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro. J Pharm Pharmacol. 1990 Aug;42(8):553-557.
Abstract: Extracts of the herb feverfew inhibit human blood platelet aggregation and secretion induced by a number of agents in-vitro and this may relate to the beneficial effects of feverfew in migraine. We previously identified several compounds with antisecretory activity in human blood platelets using adrenaline as the stimulant. In the present study, we have compared the inhibitory activity of one of these compounds, parthenolide, with that of crude feverfew extract. The effects of both on [14C]5-HT secretion from platelets and on platelet aggregation induced by a number of different stimulants were determined. The activating agents studied included the phorbol ester PMA, ADP, arachidonic acid, collagen, the thromboxane mimetic U46619, the calcium ionophore A23187, the diacylglycerol analogue OAG and adrenaline. The results show that there are marked similarities between the effects of feverfew extract and of parthenolide on both [14C]5-HT secretion and platelet aggregation, which is consistent with the effects of feverfew extract on platelets being brought about by parthenolide or similar compounds in the extract. Only in one case, when A23187 was used as the stimulatory agent, was there any discrepancy, which may have been due to materials in the extract other than parthenolide. Both feverfew extract and parthenolide were more effective as inhibitors of the [14C]5-HT secretion and aggregation induced by some agents and not others, and were most effective as inhibitors of the [14C]5-HT secretion (but not the aggregation) induced by PMA. This suggests that the effects of feverfew/parthenolide on the protein kinase C pathway warrants further study.

Kelley J, Miller RE. Hepatic necrosis following halothane anesthesia.  Ala J Med Sci. 1968 Apr;5(2):204-208.

Leak JA. Herbal medicine: Is it an alternative or an unknown? A brief review of popular herbals used by patients in a pain and symptom management practice setting. Current Review of Pain. 1999; 3:226-236.

McLeskey CH, Meyer TA, Baisden CE, Gloyna DF, Roberson CR. The incidence of herbal and selected nutraceutical use in surgical patients. Annual Meeting of American Society of Anesthesiologists (ASA) October 1999.
Abstract: An estimated 60 million American adults are reported to use herbal products. Consumers assume, because these products are natural, they are harmless. However, reports of allergic reactions, adverse effects and drug-herb interactions are surfacing. Following IRB approval, a questionnaire was given to 979 presurgical patients. Subjects were asked to indicate the amount and duration of products taken. Age and surgical procedure were noted. 170 surgical patients (17.4%) reported taking such products. Median age of herb users and non-users was 62 years. Of the patients taking these agents, 55% took only one product, 45% took multiple products. In decreasing order, the most commonly utilized herbs among this group were: gingko biloba (32.4%), garlic (26.5%), ginger (26.5%), ginseng and St. John's Wort (14%). Nutraceuticals most widely used were glucosamine (17%), chromium picolinate (17%) and chondroitin (12%). Over 40 herbs were listed as occasionally taken. Females represented 63% of herbal users and 54% of non-users (p=0.05). 19.3% of female patients took one or more of these products vs. 14.5% of male patients. Neurosurgical, gynecologic and orthopedic surgical patients' use of herbals was slightly higher than other surgical groups at 21%, 21% and 20%. Recently one-third of the American public has been identified as users of herbal products. Our lower incidence may result from reluctance of patients to admit taking such products or lack of understanding among patients regarding drug intake and contents of these products. Anesthesia providers, surgeons, and patients should be aware that these medications may not be harmless and are in increasing use. Adverse effects and drug-herbal interactions may suggest alterations in an anesthetic plan.

Murphy JM. Preoperative considerations with herbal medicines. AORN J. 1999 Jan;69(1):173-5, 177-178, 180-183.

Phillips S, Ruggier R, Hutchinson SE. Zingiber officinale (ginger)-an antiemetic for day case surgery. Anaesthesia Aug;48(8):715-717.
Abstract: The effect of powdered ginger root was compared with metoclopramide and placebo. In a prospective, randomised, double-blind trial the incidence of postoperative nausea and vomiting was measured in 120 women presenting for elective laparoscopic gynaecological surgery on a day stay basis. The incidence of nausea and vomiting was similar in patients given metoclopramide and ginger (27% and 21%) and less than in those who received placebo (41%). The requirement for postoperative antiemetics was lower in those patients receiving ginger. The requirements for postoperative analgesia, recovery time and time until discharge were the same in all groups. There was no difference in the incidence of possible side effects such as sedation, abnormal movement, itch and visual disturbance between the three groups. Zingiber officinale is an effective and promising prophylactic antiemetic, which may be especially useful for day case surgery.

Shin HC, Park HJ, Raymond SA. Potentiation by capsaicin of lidocaine's phasic impulse block in isolated rat sciatic nerve. Pharmacol Res 1994 Jul;30(1):73-79.
Abstract: Compound action potentials (CAPs) of A- and C-fibres were recorded from isolated sciatic nerves of the rat to determine whether lidocaine-induced phasic impulse block was affected by low doses of capsaicin. Preceding impulse activity produced phasic reductions of the amplitudes of both A- (5.7 +/- 1.3%) and C-CAPs (20.7 +/- 7.0%) in drug-free solution. Capsaicin alone (50 microM) did not change the activity-induced reductions of the heights of both CAPs (A-CAP: 6.2 +/- 1.7%, C-CAP: 22.3 +/- 8.0%). Lidocaine (100 microM) caused differential phasic blocks between the A-CAP (20.1 +/- 3.7%; n = 7) and the C-CAP (33.8 +/- 4.9% n = 7). Lidocaine's phasic impulse block was potentiated after 30 min of subsequent capsaicin administration (A-CAP: 40.6 +/- 4.7%, n = 7; C-CAP: 48.8 +/- 5.5% n = 9). Capsaicin's phasic potentiating effects were reversed after 30 min of washing. These results suggest that capsaicin may be a useful agent for the reversible potentiation of phasic impulse blockade by lidocaine.

Voelker R. Herbs and Anesthesia. JAMA, 281(20).May 26, 1999.1882.