Department of Anaesthesia and Intensive Care, Pinderfields General Hospital, Aberford Road, Wakefield, West Yorkshire WF1 4DG, UK
* Corresponding author. E-mail: christina{at}feelingsleepy.com
Accepted for publication September 3, 2004.
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Abstract |
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Keywords: analgesics opioid, remifentanil ; complications, infection, tetanus
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Introduction |
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Case report |
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Nine days later she presented with a right upper motor neurone facial nerve palsy and, with a presumed diagnosis of Bell's palsy, was prescribed a course of steroids. Following treatment, she developed a local infection around the original wound with severe trismus. She was admitted for rehydration, i.v. antibiotics (co-fluampicil 250 mg/250 mg qds) and investigated further. Thirteen days following the initial injury, whilst still an in-patient, she collapsed and suffered a 15-s period of apnoea. She re-started breathing after use of basic airway manoeuvres and suction. A diagnosis of cephalic tetanus progressing to generalized tetanus was made.
The patient was taken to an anaesthetic room for stabilization before transfer to the intensive care unit (ICU). Following insertion of a radial arterial catheter, she was electively intubated using a rapid sequence induction technique. The patient was then sedated with propofol (05 mg kg1 h1) and alfentanil (02.5 mg h1) infusions, given boluses of midazolam (0.10.2 mg kg1) to control the spasms, and paralysed with boluses of the non-depolarizing neuromuscular blocking agent atracurium (0.5 mg kg1), while further invasive monitoring was established. During this period, she suffered a period of fast atrial fibrillation at a rate of 170200 beat min1, and a mean arterial pressure of 30 mm Hg. This spontaneously reverted to sinus rhythm after 90 s, and once stable the patient was transferred to the ICU. Here she was given a bolus of tetanus immune globulin (150 u kg1 i.m.), and a magnesium sulphate infusion was commenced (010 mmol h1, titrated to maintain plasma magnesium at 24 mmol litre1). She was also prescribed i.v. metronidazole (500 mg tds) for 7 days. The wound on the right temple was surgically debrided following transfer to the ICU.
The patient remained haemodynamically stable during her ICU admission with no signs of autonomic instability. However, she continued to have severe generalized spasms occurring spontaneously and triggered by the most minor stimuli. She was ventilated using a pressure control mode with tidal volumes of 57 ml kg1. Between spasms, artificial ventilation was achieved satisfactorily. However, during a spasm, tidal volumes dropped to less than 1 ml kg1, and manual bagging was impossible because of chest wall rigidity. With frequent and often prolonged spasms, this caused major problems in administering basic intensive care, and made physiotherapy almost impossible. Gas exchange worsened and oxygen requirements increased.
Initially the spasms were managed with propofol, alfentanil, midazolam (010 mg h1), and magnesium sulphate infusions along with boluses of atracurium when required. However, even with maximum doses of this therapy, the spasms remained problematical. On day 2, the alfentanil and midazolam infusions were discontinued along with the atracurium boluses, and a remifentanil infusion was started at a rate of 0.050.1 µg kg1 min1 as an adjunct to sedation and for analgesia. The infusion rate was increased 1 min before any therapy, and titrated to effect (0.30.6 µg kg1 min1). This controlled spasms sufficiently to allow therapy to continue without the need for neuromuscular block or the use of benzodiazepines, and allowed the propofol to be reduced to 0.52.0 mg kg1 h1. The patient remained haemodynamically stable with this infusion regimen. When the remifentanil infusion was in progress and the spasms were controlled, the magnesium sulphate infusion was also stopped. The spasms did not worsen after stopping the magnesium. On day 2, an elective percutaneous tracheostomy was performed with propofol sedation, remifentanil, and local anaesthetic infiltration of the skin (lidocaine 2% with 1:200 000 epinephrine).
The propofol and remifentanil infusions were stopped on a regular basis to ensure optimal sedation levels and to monitor progress of the disease. The spasms gradually reduced both in frequency and severity, allowing the propofol and remifentanil infusion rates to be reduced. After 2 weeks of intensive care, the tetanic spasms had ceased and the propofol and remifentanil infusions were successfully discontinued. However, with cessation of sedation, the patient showed no conscious response to stimuli and decerebrate posturing. There was also spontaneous facial twitching. She could not be weaned from ventilatory support. An EEG performed on day 8, whilst the patient was sedated, had shown alternating slow wave activity and periods of suppression, attributable to her sedated state. No epileptiform activity was seen. However, with the history of a respiratory arrest and a period of haemodynamic compromise shortly before transfer to the ICU, we were concerned that the patient may have sustained a hypoxic brain injury. On day 17, cerebral function monitoring was commenced, which showed epileptiform activity. After a loading dose of phenytoin (1 g as an i.v. infusion over 20 min) both the seizure activity seen on the cerebral function monitor and the facial twitching stopped. At this time, the patient also developed severe bronchopneumonia, and in view of this and the cerebral function findings, treatment was not increased. The patient died on day 18. Subsequent post-mortem examination showed evidence of hypoxic brain injury.
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Discussion |
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Since the widespread immunization programme introduced in 1961, tetanus has become a rare disease in the UK. Vaccination guidelines are widely available.2 Omission of the tetanus booster in this case follows current guidelines for the management of tetanus-prone wounds, but with no booster having been given for 20 yr, the patient's immunity should have been considered further. In this case, the diagnosis was delayed. This was because the patient initially presented with a facial nerve palsy. This was treated and, when she then developed trismus, more common causes of this were investigated first. Cephalic tetanus, when a cranial nerve is affected leading to a localized motor weakness (in this case, the facial nerve) is a rare form of tetanus and is associated with a poor prognosis, especially if it progresses to generalized tetanus.
A review article3 comprehensively discussed the presentation and management of tetanus, which has traditionally been with sedation, anticonvulsants, neuromuscular blocking agents, and intermittent positive pressure ventilation. However, this approach is associated with a degree of morbidity and mortality,4 5 and different methods to control the spasms have been sought including magnesium sulphate infusions,6 dantrolene infusions,7 and intrathecal administration of baclofen.8 9 The mainstay of control of rigidity and spasms is sedation with a benzodiazepine,3 and in this case midazolam was used. Anticonvulsants are also used for additional sedation, particularly phenobarbitone.3 There were supply problems with phenobarbitone in this case and whilst waiting for the drug to arrive, and in the face of worsening spasms, the remifentanil was started. When an EEG on day 8 did not show any epileptiform activity, anticonvulsants were not added as spasms were being controlled.
Remifentanil, a phenylpiperidine derivative, is a selective mu-opioid receptor agonist, which has recently been licensed for use in critical care. It has an established role in neurosurgical intensive care,10 and is becoming established within cardiac and general intensive care.11 Remifentanil has a rapid onset of action and is metabolized by non-specific ester hydrolysis in the blood and tissues. It has a short clinical duration of action (35 min) independent of the duration of infusion.12 As such, its half time is context-insensitive, allowing precise titration of infusion rates.
In this case, a maintenance infusion dose of remifentanil was sufficient to provide analgesia and tolerance of artificial ventilation. Increasing the infusion rate 1 min before therapy proved successful in controlling spasms and with titration of the dose, procedures such as physiotherapy could be performed. There was also a rapid fall in oxygen requirements (from 0.6 to 0.3). On day 2 of the remifentanil infusion, we successfully performed a percutaneous tracheostomy using propofol sedation and an increase in the infusion rate of remifentanil (0.5 µg kg1 min1) with local anaesthetic infiltration of the skin. Gupta and colleagues13 report the routine use of this technique in general intensive care, and note excellent haemodynamic stability during procedures.
Tetanic spasms are extremely painful and may be so severe as to cause fractures and tendon avulsions. Remifentanil is known to be a highly effective analgesic with recent work suggesting it inhibits muscular pain to a greater degree than cutaneous pain in human volunteers.14 It also has fewer of the side-effects seen with the agents commonly used for sedation in the ICU.15 With its rapid metabolism it is non-cumulative even in patients with hepatic or renal failure,16 17 a problem seen with other such agents and their metabolites.
Potential problems do exist with the use of remifentanil. It is expensive but appears to have a sparing effect on other drugs. With tetanus being primarily a disease of the developing world, access to this new drug in the areas where the disease is more commonly seen may be limited by its cost. One of the side-effects of remifentanil is muscle rigidity,12 but this did not cause any problems with chest wall compliance or ventilation in this case. Remifentanil by infusion is also associated with hypotension and bradycardia, both of which are undesirable in a patient already prone to cardiovascular instability by the nature of the disease. In this case, autonomic instability was not problematical either before or during the infusion. However, remifentanil should be used with caution to avoid this side-effect. Tolerance is also a side-effect of the opiates. Evidence for the development of tolerance following a remifentanil infusion is conflicting, and studies have only examined tolerance following short (less than 3 h) periods of use. One study18 found a profound and rapid decline in the analgesic effect of remifentanil and a corresponding increase in opioid requirements, but subsequent studies19 20 found no clinical evidence of acute opioid tolerance.
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References |
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2 British National Formulary Number 47. British Medical Association and Royal Pharmaceutical Society of Great Britain: Pharmaceutical Press, March 2004; 59293
3 Cook TM, Protheroe RT, Handel JM. Tetanus: a review of the literature. Br J Anaesth 2001; 87: 47787
4 Edmondson RS, Flowers MW. Intensive care in tetanus; management, complications, and mortality in 100 cases. Br Med J 1979; 1: 14014[ISI][Medline]
5 Appadu BL, Greiff JMC, Thompson JP. Postal survey on the long-term use of neuromuscular block in the intensive care. Intensive Care Med 1996; 22: 86266[CrossRef][ISI][Medline]
6 Attygalle D, Rodrigo N. Magnesium as first line therapy in the management of tetanus: a prospective study of 40 patients. Anaesthesia 2002; 57: 778817[ISI][Medline]
7 Checketts MR, White RJ. Avoidance of intermittent positive pressure ventilation in tetanus with dantrolene therapy. Anaesthesia 1993; 48: 96971[ISI][Medline]
8 Dressnandt J, Konstanzer A, Weinzierl FX, Pfab R, Klingelhöfer J. Intrathecal baclofen in tetanus: four cases and a review of reported cases. Intensive Care Med 1997; 23: 896902[CrossRef][ISI][Medline]
9 Saissy JM, Demaziere J, Vitris M, et al. Treatment of severe tetanus by intrathecal injections of baclofen without artificial ventilation. Intensive Care Med 1992; 18: 2414[ISI][Medline]
10 Tipps LB, Coplin WM, Murry KR, Rhoney DH. Safety and feasibility of continuous infusion of remifentanil in the neurosurgical intensive care unit. Neurosurgery 2000; 46: 596602[ISI][Medline]
11 Cohen J, Royston D. Remifentanil. Curr Opin Crit Care 2001; 7: 22731[CrossRef][Medline]
12 Egan TD. Remifentanil pharmacokinetics and pharmacodynamics. A preliminary appraisal. Clin Pharmacokinet 1995; 29: 8094[ISI][Medline]
13 Gupta A, Ravalia A. Remifentanil for percutaneous tracheostomies in ITU. Anaesthesia 2000; 55: 49192
14 Curatolo M, Petersen-Felix S, Gerber A, Arendt-Nielsen L. Remifentanil inhibits muscular more than cutaneous pain in humans. Br J Anaesth 2000; 85: 52932
15 Murdoch S, Cohen A. Intensive care sedation: a review of current British practice. Intensive Care Med 2000; 26: 92228[CrossRef][ISI][Medline]
16 Dershwitz M, Hoke JF, Rosow CE, et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology 1996; 84: 81220[CrossRef][ISI][Medline]
17 Hoke JF, Shlugman D, Dershwitz M et al. Pharmacokinetics and pharmacodynamics of remifentanil in persons with renal failure compared with healthy volunteers. Anesthesiology 1997; 87: 53341[CrossRef][ISI][Medline]
18 Vinik HR, Kissin I. Rapid development of tolerance during remifentanil infusion in humans. Anesth Analg 1998; 86: 130711[Abstract]
19 Cortínez LI, Brandes V, Muñoz HR, Guerrero ME, Mur M. No clinical evidence of acute opioid tolerance after remifentanil-based anaesthesia. Br J Anaesth 2001; 87: 8669
20 Gustorff B, Nahlik G, Hoerauf K, Kress HG. No early tolerance during remifentanil infusion in volunteers. Eur J Anaesthesiol 2001; 18 (Suppl 21): 138138 (abstract A494)