Blog with interesting cases and/or problems related to anesthesia with discussion based on best evidence in the literature.

August 31, 2013

Severe dystonic reaction to preoperative Reglan administration

A 50 year old Female undergoing routine surgery is given Reglan to prevent PONV.  After surgery, she is noticed to have severe grimmacing, or contraction of her facial muscles.  She is unable to control this and after receiving 1 mg Cogentin, she improves.

My observation is that my fellow colleagues routinely administer IV reglan 10 mg to patients as they roll back.  It seems to be a part of the routine preoperative cocktail that usually includes 2 mg of versed, some fentanyl and maybe glycopyrrolate.  I've thought this odd, but since I seem to be the odd man out in regards to its use, I usually don't say anything.  In some cases, when I arrive to take over a case, and my partner or the CRNA has prepared the room for the case, they hand me syringes one of which is always reglan 10 mg.

The main reason to give Reglan 10 mg to an otherwise healthy patient is presumably for prophylaxis against PONV.  The other thing I notice is ubiquitous use of zofran as well.  This seems to be used for virtually all patients.

PONV is a significant problem in the anesthesia world for which we have yet to find a cost effective preventative method that is void of side effects.  While avoiding PONV by utilizing preventative therapies can be cost effective, and very important to patients, carelessly treating all patients equally in this domain seems counter productive.  Apfel et al. created a simple scoring system that was validated for inpatients undergoing surgery.  The beauty of this scoring system is its simplicity making it useful at the bedside.  To determine a patient's risk for PONV, add one point for each of the following criteria:

  • Non smoker
  • Female
  • History of PONV or History of motion sickness
  • required use of opioid pain medications after surgery
The predicted risk of PONV is as follows:
0 points-10%
1 point-  20%
2 points- 40%
3 points- 60%
4 points- 80%

Patients with low risk (i.e. 0 to 1 points) really don't require prophylaxis.  A better way of stating this, is that the risks of adverse affects probably outweigh the benefit from the medication.  If prophylaxis is given, the best option is probably decadron at 4 to 8 mg. At this dosage, its side effect profile is favorable.  Dexamethasone should always be first line for prophylaxis for PONV for two reasons (unless contraindicated). 1)  it is not considered effective for established PONV, and 2) Apfel in a head to head trial demonstrated that it is just as effective as Zofran (doses of 4 mg vs 4 mg) when used for prophylaxis [4].

Furthermore, dexamethasone has been shown to reduce pain scores and even improve outcomes at dosages around 8 mg [1,2.3].

Metoclopramide has a long history of utilization in anesthesia for prevention and treatment of PONV.  Metoclopramide, a benzamide derivative,  is primarily a D2 antagonist, but also enhances release of acetylcholine.   As seen in this slide on the receptors involved in PONV, metoclopramide should be efficacious in theory.  (see fig).

Metoclopramide was established as a go to prophylactic anti emetic when Rao showed a zero incidence of PONV after pretreatment with oral Metoclopramide prior to surgery in 1982[5].  Others have also found a benefit with oral Metoclopramide in the 1970's and 1980s.  However, recently, several studies and meta analysis has demonstrated that metoclopramide does not prevent PONV better than placebo with increased side effects compared to zofran [6-8].  More recently, Wallenborn and associates were able to find an improvement in PONV symptoms when 25 to 50 mg of metoclopramide was used plus decadron 8mg, but not at a dose of 10 mg.  They concluded, that, "Although the addition of 10 mg metoclopramide to dexamethasone is a standard prophylaxis for postoperative nausea and vomiting in Germany, we think that this dosage is suboptimal."  However, use of metoclopramide has continued despite the recent publications indicating lack of efficacy.  And now, the previous systematic review published by Tramer and associates has been called into question.  The issue brought to our attention by Kranke and Apfel was that a large number of the studies included in the meta analysis by Tramer were contributed by one researcher by the name of Yoshitaka Fujii.  This fraud resulted in a recall of his work on PONV with metoclopramide and several of the Anti 5HT3s.  A review of the literature after eliminating these articles (those contributed by Yoshitaka), produced a different light on Metoclopramide. De Oliveira's analysis revealed a NNT of 7.6 in preventing early PONV, but an NNT of 10.5 for the prevention of early vomiting.
      More concerning is that there are other reports of significant side effects as described above in patients receiving this medication.  In one report an otherwise healthy 21 year old female developed severe dysphoria, agitation, and akathisia following metoclopramide administration.  Another report describes severe rigidity, generalized tremor, and opisthotonos after IV metoclopramide 10 mg.  The authors of these case reports also related many other instances of akathasia or increased anxiety after metoclopramide administration.
An Acute dystonic reaction consists of facial grimmacing, intermittent torticollis and abnormal eye movements (oculogyric crisis).  These acute dystonic reactions are often associated with medications such as metoclopramide given as antiemetics. Unfortunately, the etiology of this syndrome is unknown, but seems to be related to an imbalance of dopaminergic vs cholinergic neurotransimission in the CNS.  Parkinsonism shares many similar characteristics of acute dystonic reactions.  So it is not surprising that Cogentin has found benefit in both conditions.  In general, CNS inhibition of dopaminergic neurotransmission by either medication (anti dopaminergics) or pathological loss of dopaminergic neurons, leads to a relative abundance of cholinergic neurotransimission.  Blockade of this cholinergic neurotransmission brings a balance back to the CNS.  Diphenhydramine (Bendadryl) or Benztropine (Cogentin) are useful for this purpose.  Although a diagnosis is often obvious in the context , a quick review of other potential diagnoses is relevant. Tetanus and strychnine poisoning could present with similar symptoms.  Hyperventilation can result in muscular spasms (carpopedal). Hypocalcemia and hypomagnesemia can cause severe muscular spasms as well.  Lastly, the clinician might consider a primary neurological disease and perhaps rule this out given the proper history.  It is not uncommon for clinicians to confuse an acute dystonic reaction witha seizure.  To rule out seizure it is important to verify that indeed the patient can follow commands.
The take away message is that anesthesiologists and other anesthesia providers often are careless, perhaps, sloppy in their approach to PONV in general.  The carefree use of metoclopramide in everyday practice highlights this.  Although the chances of encountering a dystonic reaction or other side effect from metoclopramide, using it in a carefree way without a clear understanding of how you are benefiting the patient borders on malpractice.  Alas, remember, "primum non nocere", or, first, do no harm!

Most reviews on approaching a surgical patient in terms of prevention of PONV indicate that determining the patient's risk is the first step using a validated scoring method.  Low risk patients should not receive prophylaxis.  Moderate risk patients should receive one antiemetic medication as prophylaxis, and this should be dexamethasone as described above.  High risk patients should have a well thought out plan.  While ondansetron is likely given as a prophylactic dose in most of these patients, there is evidence that perhaps it should be held for treatment instead.  Tramer et al[10]. looked at Ondansetron in a systematic review and showed that for 100 patients treated with prophylactic Ondansetron, 20 would be prevented from vomiting, but 3 would have elevated liver enzymes and 3 more would develop headaches from this treatment.  Ondansetron was more effective in treating established PONV.  Furthermore, the chances of developing a headache from Ondansetron was dose related (higher dose, more likely chance of headache).   Tramer also showed that the prophylactic antiemetic effect is comparable to using a propofol infusion or simply omitting nitrous oxide.  Therefore, in my practice, when it's feasible, I use a propofol infusion (and avoid nitrous), in the highest risk patients and save Ondansetron for treatment.  I always give provide prophylactic dexamethasone, and perhaps a scopolamine patch as prophylaxis in high risk individuals.

1. Diakos EA et al.  Dexamethasone reduces pain, vomiting and overall complications following tonsillectomy in adults: a systematic review and meta-analysis of randomized controlled trials.  Clin Otolaryngol. 2011; 36. 531-42.
2. Bisgaard T, Rosenberg J, et al.  Preoperative dexamethasone improves surgical outcome after Lap Cholecystectomy.  Annals of Surg. 2003; 5. 651-60.
3.  De Oliveira GS et al.  Perioperative Single Dose Systemic Dexamethasone for Postoperative Pain:  A meta-analysis of Randomized controlled Trials.  Anesthesiol. 2011; 115:  575-88.
4.  Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of postoperaative nausea and vomiting.  N Engl J Med.  2004;350: 2441-51.
5.  Rao TLK, Suseela M, El-ETr AA.  Metoclopramide and cimetidine to reduce gastric juice pH volume. Anesth Analg. 1984;63:S264.
6.  Domino KB, Anderson EA, Polissar NL, Posner KL.  Comparative efficacy and safety of Ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis.  Anesth Analg. 1999;88:1370.
7.  Henzi I, Walder B, Tramer MR.  Metoclopramide in the prevention of postoperative nausea and vomiting:  a quantitative systemic review of randomized, placebo-controlled studies.  Br J Anaesth. 1999; 83:761-71.
8.  Farhat K et al.  Comparison of Ondansetron and Metoclopramide for PONV Prophylaxis in Lap Cholecystectomy.  J Anesthe Clinic Res. 2013;4(3): 1-4.
9.  Wallenborn J et al.  Prevention of postoperative nausea and vomiting by metoclopramide combined with dexamethasone: randomized double blind multicenter trial.  BMJ. 2006; 333:324.
10. Tramer MR et al.  Efficacy, Dose-Response, and Safety of Ondansetron in Prevention of Postoperative Nausea and Vomiting:  A Quantitative systematic review of randomized placebo-controlled trials.  Anesthesiol. 1997; 87: 1277-89.

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