Minimum alveolar concentration for halothane in children with cerebral palsy and severe mental retardation

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1 Minimum alveolar concentration for halothane in children with cerebral palsy and severe mental retardation F. J. Frei, 1 M. H. Haemmerle, 1 R. Brunner 2 and C. Kern 3 1 Department of Anaesthesia, and 2 Department of Orthopaedic Surgery, University Children s Hospital, Römergasse 8, Postfach, CH-4005 Basel, Switzerland 3 Department of Anaesthesia, University Hospital, CH-4031 Basel, Switzerland Summary Children with cerebral palsy and severe mental retardation who present for operation may require lower concentrations of inhalational anaesthetics than healthy children. The minimum alveolar concentration (MAC) for halothane was measured in 36 children and adolescents, aged 4 18 years, who underwent orthopaedic surgery. The control group consisted of 12 healthy children (group 1). Children with cerebral palsy and severe mental retardation were allocated to one of two groups: those taking chronic anticonvulsant medication (group 2) (n ¼ 12) and those who did not take any drugs (group 3) (n ¼ 12). The mean (SEM) MAC value for halothane (expressed in volume per cent) was 0.90 (0.02) for healthy children. Children with cerebral palsy had significantly lower MAC values whether they took anticonvulsant drugs or not (0.62 (0.03) and 0.71 (0.10), respectively). Keywords Anaesthesia; paediatric. Anaesthetics, volatile; halothane. Complications; cerebral palsy. Potency; minimal alveolar concentration.... Correspondence to: Dr F. J. Frei Accepted: 7 December 1996 In paediatric medicine, the term cerebral palsy is used to describe a group of diverse nonprogressive syndromes that affect the brain and impair motor function; onset is presumed either before or at the time of birth, or in early childhood. Many factors, both genetic and acquired, have been postulated as causes of cerebral palsy. These include infections, trauma, toxins, prematurity, maternal toxaemia and intraventricular haemorrhage [1]. However, the aetiology remains obscure in many cases. One-third of patients with cerebral palsy have severe mental retardation [2] and another third develop a seizure disorder [3]. In patients with cerebral palsy, the response to anaesthetic drugs is thought to be less predictable than that of healthy children [4]. Based on our clinical experience we felt that these children need lower concentrations of inhalational anaesthetics than healthy children to reach a similar depth of anaesthesia. The cause of this difference could be the underlying disease itself or, in seizure patients, anticonvulsant drugs. We measured the minimum alveolar concentration (MAC) of halothane in children with cerebral palsy and severe mental retardation who were, or who were not, taking anticonvulsant drugs. Methods Three groups of patients between 4 and 18 years of age were investigated. Group 1 (control group) comprised 12 normal, healthy children, whereas groups 2 and 3 each consisted of 12 children who had cerebral palsy associated with severe mental retardation. Patients in group 2 took anticonvulsant medication but those in group 3 did not. Severe mental retardation was defined as the inability to express meaningful words or sentences, or follow verbal commands (show your tongue, close your eyes). Children with gastro-oesophageal reflux or significant cardiac or pulmonary disease were not studied. The study was approved by the ethics committee of the hospital and informed consent was obtained from one of the parents or the legal guardian of the child. All the patients had general anaesthesia that involved tracheal Blackwell Science Ltd

2 F. J. Frei et al. Halothane in cerebral palsy intubation. The children were fasted overnight but were allowed to drink clear fluids up to 2 h before the start of anaesthesia. Pre-operatively, they did not receive any sedative drugs except their usual anticonvulsant medication (Table 1). Anaesthesia was started with increasing concentrations of halothane (up to 4% inspired concentration) in oxygen. Standard monitoring was employed and an intravenous catheter was inserted. A cuffed tracheal tube with a suction channel that ended at the tip of the tube was inserted when ventilation was controlled and anaesthesia was deemed adequate. No muscle relaxants were used. Ringer s lactate solution ml.kg ¹1 was administered to all patients during the first 15 min of anaesthesia. Temperature was measured in the distal oesophagus. A circle system was used for the anaesthetic. Inspired and expired gas concentrations were measured with a Normac gas analyser [5], which was calibrated before each study. Measurements were made at the tip of the tracheal tube by suctioning gas continuously through an in-built side channel in the tube. After tracheal intubation, ventilation was adjusted to achieve an end-tidal CO 2 partial pressure of kpa, and a preset end-tidal concentration of halothane was achieved by adjusting the inspired concentration accordingly. The patients were ventilated for 15 min at a constant end-tidal halothane concentration. The motor response to a tetanic stimulation was determined. After cleaning the skin with ether, two electrodes (Neotrode, Neonatal/Pediatric, Medtronic Andover Medical; Haverhill, MA, USA) were placed at a distance of about 3 5 cm from each other at the distal forearm over the ulnar nerve. Square-wave pulses of 0.25 ms were applied with a current of 60 ma and a frequency of 50 Hz for 5 s. The motor response was graded as positive if the patient showed a gross purposeful movement of the head or the extremities within 90 s of stimulation. Movement of the stimulated arm, breath holding, bucking or grimacing during stimulation was not considered a positive reaction [6]. The 12 patients in each group were studied consecutively and the MAC values were calculated with the up and down method [7]. The first patient in every group was stimulated at a concentration of 0.76% halothane; the following patients were stimulated at preset concentrations with a constant logarithmic interval (e þ (0 ¹ ) ; e þ (1 ¹ ) ; etc., equivalent to 1.10; 0.97; 0.86; 0.76; 0.67; 0.59; and 0.52%). To determine the standard error of MAC, we divided each group into three subgroups of four patients each and calculated the mean anaesthetic concentration for each subgroup. The standard error was the square root of the variance of the mean halothane concentration of these three subgroups. Statistical significance (p < 0.05) was determined using repeated-measures of analysis of variance and the Student Newman Keuls multiple range test. Results Patients details are shown in Table 1. Although the mean body weight was higher and the mean age was lower in healthy children compared with those with cerebral palsy, these differences were not statistically significant. At the time of tetanic stimulation, mean (SD) oesophageal temperatures were 35.8 C (0.7), 35.7 C (0.8) and 35.9 C (0.6) in groups 1, 2 and 3, respectively. Atropine was administered intravenously because of bradycardia and hypotension in three patients and suxamethonium was given intravenously because of partial laryngospasm after attempted tracheal intubation in two patients. These patients were included in the study after return of the twitch response. The motor responses to the tetanic stimulus are shown in Fig. 1. Mean (SEM) calculated MAC values were 0.90 (0.02), 0.62 (0.03) and 0.71 (0.10) for normal children, children with cerebral palsy who took anticonvulsant drugs and affected children who did not take anticonvulsant drugs, respectively. The responses in group 1 were statistically different from those in groups 2 and 3. Discussion We found significantly lower MAC values for halothane in children with cerebral palsy associated with severe mental retardation compared with normal control patients. Children with cerebral palsy who did not take seizure medication had slightly higher MAC values than children who took anticonvulsant drugs, but this difference was not statistically significant. Tetanic stimulation of the ulnar nerve has been used as a substitute for surgical incision. In humans, resulting MAC values have slightly underestimated MAC values obtained by surgical incision [8]. In our study, MAC values for halothane measured with tetanic stimulation in normal children concurred with known values of % measured by the surgical incision technique [9, 10]. Hypothermia decreases MAC by approximately 5% per 1 C [11] but although body temperature decreased slightly during the equilibration period, it did not differ among the groups. Cerebral palsy is a term which is applied to some central nervous system disorders in which various brain regions are affected. Gross malformations are found in only about one-third of autopsied children but microscopic cortical or subcortical changes in various areas of the brain are 1997 Blackwell Science Ltd 1057

3 F. J. Frei et al. Halothane in cerebral palsy Anaesthesia, 1997, 52, pages Table 1 Patient details. Age Weight (years) (kg) Gender Underlying disease Symptoms Medication Group f f f m m f m m f m m m mean SD Group m lissencephaly hypotonic tetraparesis primidone, valproic acid m perinatal asphyxia spastic tetraparesis diazepam f atrophy left hemisphere spastic tetraparesis phenobarbitone m congenital brain damage spastic tetraparesis phenytoin m perinatal brain damage caused by an infection spastic tetraparesis valproic acid m congenital cytomegaly spastic tetraparesis, left side dominant valproic acid, phenobarbitone, baclofen m perinatal asphyxia spastic tetraparesis, athetosis primidon m perinatal asphyxia spastic tetraparesis valproic acid, diazepam m cerebral palsy since birth, aetiology unclear spastic tetraparesis valproic acid, clobazepam m cerebral palsy since birth, aetiology unclear spastic tetraparesis clobazepam, phenobarbitone, valproic acid f intraventricular haemorrhage spastic tetraparesis phenytoin m cerebral palsy since birth, aetiology unclear spastic tetraparesis valproic acid, clobazepam mean SD Group f prolonged fit age 5 months spastic tetraparesis f perinatal asphyxia spastic tetraparesis m perinatal asphyxia spastic tetraparesis m unknown cause, normal birth nonspastic tetraparesis f prematurity, 32 gestational weeks, cause of brain damage unknown spastic tetraparesis m cardiac arrest age 5 months, unknown cause spastic tetraparesis f meningitis in infancy spastic tetraparesis f prematurity, 35 gestational weeks, periventricular leucomalacia spastic tetraparesis m hydrocephalus at birth spastic tetraparesis m prematurity, 32 gestational weeks, perinatal asphyxia spastic tetraparesis m perinatal asphyxia spastic tetraparesis, athetosis m cerebral palsy since birth, aetiology unclear spastic tetraparesis mean SD Blackwell Science Ltd

4 F. J. Frei et al. Halothane in cerebral palsy End-tidal concentration (%) Motor response Healthy patients Figure 1 Patient details of 36 children undergoing orthopaedic operations under general anaesthesia with halothane. The 12 patients in each group were studied sequentially (numbers above and below the bars) using the up and down method (see text for further details). Group 1, healthy children; group 2, children with cerebral palsy taking medication; group 3, children with cerebral palsy not taking medication. Cerebral palsy, anticonvulsive therapy Cerebral palsy, no medication noted in others. Central sensory impairment is known to occur in cerebral palsy patients with hemiplegia [1]. It is reasonable to assume that this is probably also the case in patients with tetraplegia, although this has not been investigated systematically in children. However, in 25% of 123 adult patients with developmental disabilities, there was a significantly elevated pain threshold. Those with more severe mental retardation were also more likely to display signs of pain insensitivity or indifference [12]. This decreased pain perception could explain the observed decrease of MAC. In patients with severe cerebral palsy and disturbed motor function (mainly tetraparesis), the regulatory influence of motor neurones of the central nervous system on the interneurons that connect the incoming sensory fibres and the lower motor neurones in the spinal cord is dysfunctional and leads to the well-known symptoms of hyperreflexia and spasticity [13]. This pathophysiological state is of particular interest in the light of new data suggesting that anaesthetic action within the spinal cord is important in suppressing somatic responses to painful stimuli [14]. A decrease of inhibitory signals from the upper motor neurones may cause lower motor neurones to be more sensitive to inhalational anaesthetics resulting in a requirement for lower concentrations to depress the motor response to a painful stimulus. We observed a small but not significant difference in MAC between patients in groups 2 and 3. Although acute administration of barbiturates and benzodiazepines decreases MAC [15, 16], chronic administration of barbiturates has no effect on the MAC of halothane in dogs [17]. No studies have investigated the impact of other anticonvulsant medication (primidone, valproic acid, phenytoin and baclofen) on MAC values in children. Further studies of children with a seizure disorder who take a particular anticonvulsant drug but are otherwise healthy are needed. In summary, we observed a decrease in MAC values for halothane in children with cerebral palsy and severe mental retardation. Explanations for this phenomenon include decreased central pain perception or a disturbed neuronal interaction at the spinal cord level. Acknowledgments We thank Mrs Ursula Schaller and Mrs Joan Etlinger for help in the preparation of this manuscript. References 1 Wollack JB, Low NL, Carter S. Static encephalopathies. In: Abraham MR, Hoffman JIE, Rudolph CD, eds. Rudolph s Pediatrics, 19th edition. Norwalk: Appleton & Lange, 1991: Robinson RO. The frequency of other handicaps in children with cerebral palsy. Developmental Medicine and Child Neurology 1973; 15: Aksu F. Nature and prognosis of seizure in patients with cerebral palsy. Developmental Medicine and Child Neurology 1990; 32: Krane EJ, Davis PJ, Smith PM. Preoperative preparation. In: Motoyama EK, Davis PJ, eds. Smith s Anesthesia for Infants and Children. St Louis: Mosby, 1990: Zbinden AM, Westenskow D, Thomson DA, Funk B, Maertens J. A laboratory investigation of two new portable 1997 Blackwell Science Ltd 1059

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