Intra - and postoperative tremors: prevention and pharmacological treatment

Abstracts

JUSTIFICATIVA E OBJETIVOS: Os tremores podem ocorrer como um efeito adverso da intervenção cirúrgica e anestesia. A incidência de tremores pós-operatórios varia entre 6,3% e 66%. Pacientes jovens, sexo masculino, uso de agentes anestésicos halogenados e tempo prolongado de anestesia ou procedimento cirúrgico estão relacionados com tremores. Os tremores são involuntários e apresentam-se como atividade muscular oscilatória com finalidade de aumentar a produção de calor. Tremor pós-operatório é uma desagradável complicação que está relacionada com o aumento de morbidade. O tremor aumenta o metabolismo, resultando em um acréscimo de 200% a 500% no consumo de oxigênio. CONTEÚDO: Discute as causas, a prevenção e o tratamento dos tremores intra- e pós-operatório em pacientes adultos e pediátricos submetidos à intervenção cirúrgica sob anestesia geral ou do neuroeixo. CONCLUSÕES: Os tremores são, juntamente com náuseas e vômitos, causas de intenso desconforto na sala de recuperação pós-anestésica, além de potencialmente prejudiciais por gerarem aumento da demanda metabólica. Embora a presença de tremores não tenha sido diretamente relacionada com a morbidade cardíaca, a prevenção tem se tornado tema de debate e de vários artigos científicos. A prevenção e o tratamento de tremores devem ser implementados. Pacientes com reserva cardiopulmorar limitada podem sofrer com acidose láctica, dessaturação venosa mista e hipoxemia.

ANESTESIA; COMPLICAÇÕES; TREMOR

REVIEW ARTICLE

Intra- and postoperative tremors: prevention and pharmacological treatment^*

Temblores intra y postoperatorio: prevención y tratamiento farmacológico

Viviane Ferreira Albergaria; TSA^I; Michelle Nacur Lorentz; TSA^II; Frederico Augusto Soares de Lima^III

^IAnestesiologista do Corpo Clínico do Instituto Biocor; Anestesiologista e Co-Responsável pelo CET do Hospital das Clínicas da UFMG

^IIAnestesiologista do Corpo Clínico do Instituto Biocor

^IIIME₃ da Fundação Hospitalar do Estado de Minas Gerais (FHEMIG)

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Tremors can be an adverse effect of the surgical intervention and anesthesia. The incidence of postoperative tremors varies from 6.3% to 66%. Young age, male gender, the use of halogenated anesthetics, and prolonged anesthesia or surgical procedure are related with tremors. Tremors are involuntary and present as oscillating muscular activity aiming at increasing heat production. Postoperative tremors are a disagreeable complication related with increased morbidity. Tremors increase the metabolism, resulting in a 200% to 500% increase in oxygen consumption.

CONTENTS: The objective of this paper was to discuss the causes, prevention, and treatment of intra- and postoperative tremors in adults and children undergoing general anesthesia or neuroaxis anesthesia for surgical interventions.

CONCLUSIONS: Tremors, along with nausea and vomiting, cause severe discomfort in the recovery room, besides being highly prejudicial because they generate an increase in the metabolism. Although the presence of tremors has not been directly related with cardiac morbidity, its prevention has become the subject of discussion and several scientific reports. Prevention and treatment of tremors should be implemented. Patients with limited cardiovascular reserve could develop lactic acidosis, mixed venous desaturation, and hypoxemia.

Key Words: ANESTHESIA: General, regional; COMPLICATIONS: hypothermia, tremor; TREMOR: prevention, treatment.

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Los temblores pueden ocurrir como un efecto adverso de la intervención quirúrgica y anestesia. La incidencia de temblores postoperatorios varía entre 6,3% y 66%. Pacientes jóvenes, sexo masculino, uso de agentes anestésicos halogenados y tiempo prolongado de anestesia o procedimiento quirúrgico están relacionados con temblores. Los temblores son involuntarios y se presentan como actividad muscular oscilatoria con finalidad de aumentar la producción de calor. E temblor postoperatorio es una desagradable complicación que está relacionada con el aumento de la morbidez. El temblor aumenta el metabolismo resultando en un aumento de 200% a 500% en el consumo de oxígeno.

CONTENIDO: Discute las causas, prevención y tratamiento de los temblores intra y postoperatorio en pacientes adultos y pediátricos sometidos a la intervención quirúrgica bajo anestesia general o del neuroeje.

CONCLUSIONES: Los temblores son, juntamente con náuseas y vómitos, causas de intensa incomodidad en la sala de recuperación pos anestésica, además de potencialmente perjudiciales por generar un aumento de la demanda metabólica. Aunque la presencia de temblores no haya sido directamente relacionada a la morbidez cardiaca, la prevención se ha hecho tema de debate y de varios artículos científicos. La prevención y el tratamiento de temblores deben ser implementados. Pacientes con reserva cardio pulmorar limitada pueden sufrir con la acidosis láctica, falta de saturación venosa mixta e hipoxemia.

INTRODUCTION

In homeothermic species, the thermal regulation system coordinates the defenses against cold and heat, while maintaining internal body temperature within a narrow range, ideal for physiological and metabolic functions. However, the combination of anesthesia and exposure to the cold, can lead to hypothermia and tremors in surgical patients ^1,2. Since those tremors are usually self-limiting, do not become chronic, and normally do not have more serious consequences, they are often underestimated.

Postoperative tremors are frequently associated with loss of body heat, although hypothermia by itself does not fully explain them. However, they cause discomfort for the patients and sometimes can lead to complications ³.

Along with nausea and vomiting, tremors are one of the most frequent problems during the initial recovery after general anesthesia ^4,5. Tremors are very uncomfortable and psychologically stressing. They can also lead to complications, especially in patients with coronary artery disease, due to an increase in oxygen consumption (O₂) by 100% to 600%, increase production of carbon dioxide (CO₂), resulting in reduced minute ventilation, increased cardiac output ⁶, increase in circulating catecholamines (increased heart rate), besides decreasing O₂ saturation in mixed venous blood ^7-9. There can also be an increase in intracranial and intraocular pressures, interference with the ECG, pulse oximetry ¹⁰, blood pressure, increase in metabolism, and cause lactic acidosis ^7-9.

Postoperative tremors can be of two types: the first corresponds to the tremor associated with thermal regulation that is associated with vasoconstriction, being a physiological response to central or peripheral hypothermia ^11,12 that develops in the intraoperative period; the second corresponds to the tremor associated with vasodilation or tremor not associated with thermal regulation ¹³. It has been observed that tremors do not affect only hypothermic patients ^14,15 and they can also be present in patients whose temperature is normal ^2,16.17 and, on the other hand, many hypothermic patients do not develop tremors. Sessler et al. concluded that postoperative tremors are secondary to thermal regulation ¹², are caused by hypothermia, and can also affect normothermic patients who are developing fever ¹⁵. However, some tremors during labor ¹⁸ and general anesthesia ¹⁹ are not related with thermal regulation, and worsen due to undertreated pain ^8,20.

More than ten years ago, Crossley ²¹ enumerated some variables that influence the development of tremors: prolonged surgical procedures, male gender, anticholinergic agents (atropine), spontaneous ventilation, altered physical state (high ASA), more frequent in general surgical procedure than orthopedics, and blood transfusion. He also mentioned that advanced age, and the administration of propofol, alfentanil, or morphine were the most important variables in the protection against tremors.

PHYSIOPATHOLOGY

Several studies suggest that surgery-related factors, as pain and stress, contribute to the genesis of tremors ¹². The mechanisms involved with the development of tremors are complex and presumably result from adaptive evolution. There is not one pathway responsible for them; on the contrary, several mechanisms are capable to modulate thermal regulation responses ¹⁵.

Intraoperative hypothermia, besides causing severe complications, may prolong hospitalization ²², and can also be associated with a reduction in drug metabolism, delayed awakening from anesthesia, negative nitrogen balance, and tremors ²³.

The use of hypothermia as a therapeutic strategy for neuroprotection is still controversial ²⁴. Hypothermia reduces intracranial pressure, increases cerebral perfusion pressure and decreases its metabolism. However, even moderate hypothermia has undesirable side effects, such as tremors and peripheral vasoconstriction, resulting in hemodynamic instability, increase in oxygen consumption, and cerebral and myocardial ischemia.

In humans, moderate hypothermia results in better neurological recovery in patients who survive cardiorespiratory arrest ^25,26. The International Liaison Committee on Resuscitation (ILCOR) recommends its use in those cases ²⁷.

Postoperative tremors affect 5% to 65% of patients recovering from general anesthesia ⁷, and 30% of those undergoing epidural anesthesia ²⁸. They can be tremors associated with thermal regulation or due to the release of cytokines caused by the surgical procedure. Core temperature usually falls from 0.5°C to 1.5°C in the first hour after anesthetic induction. The hypothermia that develops in the first hour after induction of general ²⁹ or neuroaxial ³⁰ anesthesia results primarily from the redistribution of heat from the center to the periphery. Every anesthetic, opioid, and sedative, reduces vasoconstriction and the autonomic control of thermal regulation (tremor threshold), facilitating the development of hypothermia.

In a study of 2,595 adult patients, Crossley ²¹ detected tremors in 164 (6.5%) and identified male gender and pre-anesthetic medication with anticholinergics as risk factors. The type of anesthetic induction was not considered a risk factor in this study. Another study by Eberhat et al. ³¹ evaluated 1,340 consecutive patients who underwent surgery under general anesthesia, and observed tremors in 11.9% of them. Risk factors related with postoperative tremors were hypothermia, age, orthopedic surgeries, and prolonged surgical procedures; but age seemed the most important factor. The objective of that study was to develop an algorithm to anticipate tremors; patients undergoing surgical procedures were evaluated, excluding those who presented preoperative hypothermia or those who used drugs that could interfere with thermal regulation (clonidine, meperidine, phenothiazine). The incidence of moderate or severe tremor (grades 3 and 4) was 11.6%. The total incidence of any tremor (including grade 2) was 14.4%. Thermal regulation activity (including vasoconstriction and piloerection) was observed in 17.6%. Among these patients, only 33% complained of being cold. The work used multivariable analysis and found three independent factors that predict the development of tremors: youth, surgeries with endoprosthesis, and low core body temperature. Age was by far the most important risk factor, being responsible for more than 70% of the predictive power of the model. This was not surprising, because thermal regulation response is decreased in the elderly ¹⁵.

It is difficult to determine independent risk factors for tremors before surgery, since several variables influence postoperative thermal regulation in the case of volatile ³² or intravenous anesthetics, and sedatives ³³. Besides, almost every drug used regularly by patients (antihypertensives, those used in the treatment of diabetes, and coumarin derivatives) seems to offer significant protection against tremors. In fact, the incidence of tremors is decreased in patients taking propranolol ³⁴.

Core temperature contributes 30% to the control of tremors and vasoconstriction, while mean skin temperature contributes 20% ³⁵. Therefore, it is reasonable to assume that, in the absence of a surgical procedure, hypothermia contributes for the development of tremors and that normothermia protects against it ¹². The study demonstrated that core temperature had only a slight influence on the development of tremors when compared with age (most important factor), and was compatible with the results of other studies that demonstrated that temperature has a weak predictive power for the development of tremors ^36,37. According to the analysis of multifactorial logistic regression, core temperature was not directly related with postoperative tremors in children, while the relative change of perioperative temperature was one of three independent predictors ³⁸. However, tremors in patients whose body temperature is lower than 36°C lasted longer than in those who were warmed up ³⁹.

The study confirmed a previous work ²¹ that showed that orthopedic surgeries (especially endoprosthesis) using bone cement was an independent risk factor for the development of tremors. A possible explanation would be the release of cytokines (tumor necrosis factor-alpha and interleukin-6) stimulated by the bone cement polymethylmethacrylate ⁴⁰.

Prolonged surgeries were associated with a higher incidence of tremors. A possible explanation is that these procedures are more complex and invasive. Damaged tissue might release pyrogenic substances that change the trigger point of the thermal regulation system in the postoperative period, leading to the development of tremors ⁴¹.

Active intraoperative warming to maintain normothermia is important in the prevention of tremors ^42,43. The center of thermal regulation is in the posterior hypothalamus, and its activity is modulated by temperature receptors in the skin, visceras, and in several levels of the neuroaxis ^42,44. Every volatile anesthetic produces tremors by changing the tremor threshold ^45,46.

During anesthesia, the patient has no thermal regulation responses, because the reflex is inhibited. During recovery, the inhibition disappears and tremors appear when the temperature is below the thermal regulation threshold ⁴⁷.

TREMORS AND ANESTHESIA

Since hypothermia is one of the predictive factors for the development of tremors, and being an independent risk factor for cardiac morbidity ⁴⁸, it should be avoided, recognized, and treated. Although it might be beneficial during the intraoperative period, by decreasing metabolism and protecting vital organs from ischemia, when the patient awakes from anesthesia, adrenergic and metabolic responses of thermal regulation are activated, causing postoperative discomfort, tremors, increased bleeding, and increased incidence of infection and cardiovascular effects ⁴⁹. During the intraoperative period, the incidence of myocardial ischemia and ventricular tachycardia are similar in hypothermic and normothermic patients. On the other hand, during the postoperative period, the incidence of ventricular tachycardia and electrocardiographic changes is greater in hypothermic patients ⁴⁸. The disparity between the intra- and postoperative periods suggests that anesthesia might have a protective effect against the adverse responses to the stress caused by the cold. There are two response mechanisms of thermal regulation to hypothermia that might be harmful to the cardiovascular system: the adrenergic response with vasoconstriction associated with elevation in blood pressure, and increased metabolic demand related to tremors ^50,51. Hemodynamic responses to the vasoconstriction secondary to thermal regulation seem to be similar without anesthesia and with different concentrations of desflurane and isoflurane ⁵².

CLASSIFICATTION OF TREMORS

The degree of tremors was evaluated and classified according to a qualitative scale in the work of Crossley and Mahajan ³⁶: 0 = without tremor; 1 = without visible muscular activity but with piloerection, peripheral vasoconstriction, or both; 2 = muscular activity affecting only one muscle group; 3 = moderate muscular activity involving more than one muscle group, but without generalized tremors; and 4 = severe muscular activity involving the entire body.

PHARMACOLOGICAL PREVENTION OF TREMORS

Proper warming of the body is not always feasible. Therefore, tremors should be prevented pharmacologically in selected patients.

Several drugs have been studied for the prophylaxis and treatment of tremors, including clonidine, meperidine, ketanserin (an anti-hypertensive drug, and antagonist with high affinity for 5-HT and a₁-adrenergic receptors); doxapram (respiratory stimulant); and tramadol and other opioids ^15,53. The cholinergic system is probably among the mediators of tremors. Physostigmine, an anticholinesterase drug that crosses the blood-brain barrier, is widely used to treat the central cholinergic syndrome ⁵⁴. Studies suggest that physostigmine increases the cholinergic neurotransmission by stimulating the hypothalamus-hypophysis-adrenal axis and the medulla of the adrenal gland, inhibiting generalized thermal regulation.

Moderate hypothermia may have undesirable effects, such as tremors and vasoconstriction, and measures to prevent them in the postoperative period might be necessary. There are reports demonstrating that clonidine reduces the incidence of postoperative tremors, but the mechanism of action has not been elucidated ⁵⁴. The a₂-agonists exert their action on a₂- adrenergic and imidazolic receptors. The first ones can be found in the brain, spinal cord, and the periphery. In the brain, they are related with sedation; in the spinal cord, with analgesia. The effects of clonidine on post-synaptic a₂-receptors in the central nervous system reduces the sympathetic tonus that leads to peripheral vasodilation and hypotension ²⁴. The effects of meperidine on thermal regulation seem to involve a₂-adrenergic receptors ⁴¹.

Several drugs (meperidine, ketanserin, sufentanil, alfentanil, tramadol, physostigmine, urapidil, nefopam, doxapram, and nalbuphine) have already been tested to prevent or treat tremors ^7-9,28,55,56. Meperidine proved to be one of the most effective ^56,57, probably by acting on the thermal regulation center ⁵⁵ or through opioid receptors ¹⁵. It is possible that NMDA receptors also modulate thermal regulation in several levels ¹⁵. Ketamine, a NMDA antagonist, showed to be capable to inhibit tremors ⁵⁸.

Treatments established to prevent tremors include several drugs, such as nefopam, a benzoxazocin, that inhibits the reuptake of noradrenaline, dopamine, and serotonin. These drugs are not specific for tremors and exert their action through different mechanisms, such as decreasing the activation of the sympathetic nervous system ^9,53,59, adrenal suppression ³⁸, stimulation of opioid receptors, or influencing the serotoninergic system ^5,9,15,60.

The cholinergic system is an important pathway that can potentially influence tremors. The hypothalamus and the striated body are the regions in the brain in which physostigmine is more active ^61,62. Physostigmine is a central acting cholinesterase inhibitor that interacts with cholinergic muscarinic, serotoninergic, and endorphinergic brain receptors, as well as with µ-opioid agonists and a₂-agonists ¹⁵. Therefore, it seems to work by increasing central neurotransmission. It seems to be safe and highly effective, with very little side effects that include hemodynamic changes; however, they were not observed in the study, probably due to the slow administration (15 minutes) ^62,63.

Besides, physostigmine produced analgesia by releasing b-endorphins ⁶⁴; and postoperative pain can lead to tremors ²⁰. The dose of physostigmine is usually 2 mg ^62,63. Physostigmine reduced significantly the incidence and severity of tremors, as much as nefopam. Cholinergic pathways seem to be involved in the thermal regulation, decreasing tremors without influencing awakening from anesthesia, alertness, and postoperative recovery.

In another study, divided in two stages, Stapelfeldt et al. ²⁴ investigated the use of clonidine in 48 patients undergoing elective neurosurgery. First, they determined, in 14 patients, the dose of clonidine necessary to prevent postoperative tremors after inducing moderate hypothermia (35°C). This dose was 3 µg.kg^-1. In the second stage, they investigated whether clonidine, due to its sedative action, would delay awakening from anesthesia in neurosurgeries and, therefore, delay the neurological evaluation. Thirty-four patients who underwent neurological surgeries were randomly distributed in two groups to receive clonidine (3 µg.kg^-1) or normal saline when the dura mater began to be sutured. Inhalational anesthetics and the infusion of opioids were discontinued at that moment and propofol was administered to every patient. Recovery of patients was evaluated two hours after the end of anesthesia at the following moments: upon opening his/her eyes, when extubated, regarding obeying commands and orientation in time and space. There were no significant differences between both groups in the duration of post-anesthetic recovery. Systolic blood pressure was lower in the clonidine group, which was statistically significant; however, it was not clinically significant ²⁴. The ideal dose of clonidine has not been determined yet, but small doses may be enough to prevent tremors after moderate hypothermia.

Piper et al. ⁹ compared clonidine and nefopam in the prevention of tremors and found out that they are equally effective. However, clonidine caused more sedation and delayed awakening, suggesting that nefopam is a better prophylactic drug.

In another systematic revision, Kranke et al. ⁶⁵ described the efficacy and risks of using drugs to prevent the development of tremors. They analyzed 27 articles (1,348 adults received medication and 931 were controls). The incidence of tremors in the control group was extremely frequent (52%). Clonidine, 65 to 300 µg (1,078 patients), 12.5 to 35 mg of meperidine (250 patients), 35 to 220 mg of tramadol (250 patients), and 6.5 to 11 mg of nefopam (204 patients) were tested in at least three studies each. All of them were more effective when compared with the controls. The studies suggest that less than four patients have to receive prophylactic clonidine in order that one patient does not present tremors after the surgery. For meperidine, nefopam, and tramadol, the efficacy seemed even more convincing. The high prevalence of tremors in patients who were not treated suggests that study populations have a high risk, and might not be representative of the general population. Besides, the high prevalence in this population tends to overestimate the usefulness of therapeutic interventions. Clonidine was tested in more studies than the other drugs, which allowed the evaluation of its dose and the time of administration. To be more effective, it should be administered during induction (and not before) in doses greater than 140 µg ⁶⁵.

There were limiting factors. First, the mechanism of action against tremors of the drugs analyzed is not completely characterized. Some of them might change the tremor threshold. This has been demonstrated for meperidine ⁶⁶ and clonidine ⁶⁷. Second, it was not possible to establish predictive factors for postoperative tremors. Third, like a similar previous study ⁴¹, it was necessary to use indirect comparisons to estimate the relative efficacy of the anti-tremor interventions, since there is no gold standard that can be used as a comparison. Fourth, most of the studies had a small cohort, and only 5 of them had 50 patient or more ^68,71, and studies with small samples tend to overestimate the efficacy of the treatment. Fifth, the quality of the method used in most of the studies was not satisfactory. And sixth, the report on side effects was poor, but it does not necessarily mean that they were not present. Dal et al. ⁷² compared low doses of ketamine, meperidine, and placebo in the prophylaxis of tremors. Ninety patients, ages 18 to 65 years, physical status ASA I or II, who underwent general anesthesia for 60 to 180 minutes, were divided in 3 groups of 30 each. Group S received normal saline; Group K received ketamine (0.5 mg.kg^-1); and Group P received meperidine (20 mg) 20 minutes before surgery. The tympanic temperature of every patient was greater than 36°C and, therefore, did not require warming. The incidence of tremors was significantly lower in Groups K and P than in Group S, and there were no differences between Groups K and P. The length of time until the first request of analgesics in Group S was much smaller (12 min) than in Groups K (25 min) and P (32 min). Two hours after the end of the procedure, every patient needed analgesics. There were no differences in pain scores among the groups, using the Visual Analogic Scale (VAS), 30 minutes after the end of the surgery. Two patients in Group K had grade 2 tremors and were treated with meperidine, which was effective, probably because its mechanism of action is different, or because the dose of 0.5 mg.kg^-1 of ketamine was not enough. Patients did not present adverse effects related to ketamine. This drug might be an alternative for the prophylaxis of postoperative tremors in patients who cannot receive meperidine. Future studies might demonstrate the ideal dose of ketamine for the prophylaxis of postoperative tremors. There were no differences between Groups K and P regarding the prevention of tremors. There was no relationship between axillary temperature and the development of tremors ⁵⁸.

Ketamin is a NMDA antagonist that is effective in the prevention of tremors, probably through the thermogenesis without tremors pathway, by acting on the hypothalamus, or by a b-adrenergic effect, besides having some effect on the k receptor. A study suggested that the action of meperidine against tremors might be through k receptors, because high doses of naloxone inhibits its action (high doses inhibit mu and kappa receptors), while small doses of naloxone do not (inhibit only mu receptors) ⁵⁶. The disadvantage of meperidine is the risk of respiratory depression, nausea, and vomiting.

Rohm et al. ⁷³ investigated the effects of physostigmine in the prophylaxis of postoperative tremors, and compared it with nefopam, a drug known to be effective ⁵. Eighty-nine patients undergoing abdominal or urological surgeries were evaluated. Patients received 2 mg of physostigmine (n = 31), 10 mg of nefopam (n = 30), or normal saline (n = 28). Hemodynamic parameters and temperature were measured at induction and 5, 15, 30, and 60 minutes after arrival in the recovery room. The incidence of tremors was significantly lower after the administration of physostigmine and nefopam (9.7% and 3.3%) than with placebo (53.6%). Time of extubation, hemodynamic parameters, and tympanic temperature were similar in all groups. Only nefopam reduced significantly the incidence of postoperative nausea and vomiting. Physostigmine reduced successfully and safely the incidence and severity of tremors. This success was similar to that of nefopam and it did not delay the recovery of patients.

Another study was undertaken by Hong and Lee ⁷⁴ with patients undergoing cesarean sections with epidural anesthesia with 8 mg to 10 mg of 0.5% hyperbaric bupivacaine associated with morphine (0.1 mg or 0.2 mg), meperidine (10 mg), or just local anesthetic (LA). The incidence of tremors was greater in patients who received just LA (23.3.%). Those who received meperidine had not only the lowest incidence (3.3%), but tremors were also less severe when compared with those who received morphine (0.1 mg – 17%; 0.2 mg – 13.3%). The epidural administration of opioids can also be capable of abolishing tremors, although their mechanism of action, influencing tremor threshold, has not been established ⁷⁵. A study by Abreu et al. ⁷⁵ compared the incidence of intra- and postoperative tremors in epidural blocks with and without fentanyl. They concluded that adding 100 µg of fentanyl to the LA for the epidural block does not abolish the tremor, but reduces the incidence and severity, without increasing the incidence of nausea and vomiting.

NON-PHARMACOLOGICAL PREVENTION OF TREMORS

Tremors can be treated by warming up the patient, applying radiant heat, or drugs ⁵⁵.

Among the measures used in the maintenance of body temperature, the warm air blanket can be beneficial and cost effective ⁴³.

Simply covering the patient with a blanket was indicated as a tremor-reducing factor that did not change core temperature ⁴³. Skin temperature is not a predictive factor for tremors. However, it is unquestionable that increasing skin temperature enough can, alone, stop tremors.

TREATMENT OF POSTOPERATIVE TREMORS

The development of tremors is a frequent complication in the recovery room, and several drugs are used to treat it, although their mechanism of action have not been elucidated ⁴¹; in a meta-analysis by Kranke et al., meperidine was deemed the most effective drug for the treatment of tremors, and a dose of 25 mg reduced the recurrence of tremors nine times as often as placebo, maintaining an anti-tremor effect for at least 45 minutes. Meperidine was associated with a small increase in side effects, such as nausea, vomiting, and reduction in respiratory rate. In situations that meperidine cannot be used, the authors suggest the use of clonidine (150 µg), ketanserin (10 mg), alfentanil (0.25 mg), or doxapram (100 mg). It should be mentioned that the intraoperative maintenance of body temperature and the use of warm air blankets decreased the need of drugs for the treatment of tremors ⁷⁶.

In a study with 220 patients aiming at identifying the effective dose of meperidine for the treatment of tremors, Crossley ⁷⁶ concluded that 0.35 mg.kg^-1 is the smallest dose necessary to treat adequately postoperative tremors.

Tramadol has also been used in the past few years to treat tremors and, according to some studies, its efficacy is similar to that of meperidine ⁷⁷.

Nefopam is a central-acting analgesic benzoxacin that reduces tremors without affecting ventilation, with minimal sedation, and proven efficacy. Contrary to other drugs, it does not cause vasoconstriction, working only in the tremor pathway ⁷⁸.

TREMORS IN PEDIATRIC PATIENTS

Most of the studies on postoperative tremors are done in adults and, when they are done with children, they include a small number of patients ¹⁶. A classical work by Akin et al. ¹⁶ with 1,507 children ages 0 to 16 years, undergoing general anesthesia, was undertaken to determine the prevalence of tremors, as well as the triggers and clinical implications. After the surgery, the child was transferred to the recovery room and received oxygen by face mask. The tympanic temperature was measured, the type and duration of the surgery were recorded, as well as the method of anesthetic induction (inhalational, with sevoflurane, or intravenous, with thiopental), age, and association with caudal epidural. The temperature of the operating room and recovery room was maintained between 22°C and 23°C. Of 1,507 children, only 53 (3.5%) developed tremors. There was a statistically significant difference between children with and without tremors regarding length of surgery, body temperature, and age. The type of surgery and gender had no relationship with the prevalence of tremors. The risk of tremors increased with ages above 6 years, use of intravenous agents for induction, and surgeries lasting more than 40 minutes. In 37 out of the 53 patients, tremors improved by rewarming alone; 16 of them needed intravenous meperidine (0.35 mg.kg^-1). In this study, the prevalence of tremors in children who received thiopental for induction was significantly greater. However, since these children were older, that could have been a contributing factor. The incidence of tremors was statistically lower in children who received caudal epidural anesthesia.

PREVENTION AND TREATMENT OF TREMORS IN CHILDREN

Kranke et al. ³ proposed an algorithm for the pharmacological prevention and treatment of tremors in children based on studies done in adults, and recommended that hypothermia should be avoided. When a child developed tremor, he/she was treated by rewarming and, if there was no response, they suggested the administration of clonidine (1.5 µg.kg^-1) or meperidine (0.35 µg.kg^-1) that is, since the treatment of tremors is simple, effective, and low cost, and since prophylaxis is recommended only in high risk patients, it should not be routinely done in children. In their study, Akin et al. ¹⁶ did not consider that prophylaxis of tremors in children was necessary, due to the low incidence (3.5%), and it should be treated when present.

CONCLUSION

Prophylaxis of postoperative tremors is simple and effective. The problem is to evaluate when they should be prevented or treated. Treatment of tremors is also effective; however, many patients presented recurrence of the problem. Since the maintenance of a normal body temperature influences profoundly postoperative tremors, the use of prophylactic drugs is questioned. It seems they should be done only in special cases, such as patients in whom greater oxygen consumption would increase the risk of complications ⁶⁵.

In a study comparing several drugs isolatedly to prevent tremors, clonidine, meperidine, tramadol, and nefopam were more effective than placebo and, although the incidence of bradycardia, hypotension, and sedation are greater with clonidine, these effects were not observed in the doses used in this study.

The incidence of tremors can be predicted with moderate discriminative power using four risk factors derived from a logistic regression analysis: age (variable with the greatest predictive power), core temperature upon admission to the recovery room, prolonged surgical procedure, and orthopedic procedures.

The pharmacological prophylaxis of postoperative tremors is possible and will only be effective when the risk is too high. This raises the question whether tremors should be prevented or treated. Treatment with meperidine or clonidine is very effective. The option for prophylaxis means the unnecessary administration of drugs to several patients, exposing them to side effects. Since intraoperative body warming and maintenance of core temperature greatly influence the incidence of postoperative tremors ¹⁰, the use of pharmacological prophylaxis is questioned. Patients in whom the cardiac supply of oxygen is compromised are a special case; in these cases, pharmacological prophylaxis is preferable, and clonidine should be the rational choice because, besides the anti-tremor effect, it has a favorable effect on the heart ⁷⁹.

REFERENCES

Submitted em 19 de maio de 2006

Accepted para publicação em 23 de março de 2007

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*

Received from Instituto Biocor, Nova Lima, MG

Publication Dates

• Publication in this collection
  31 July 2007
• Date of issue
  Aug 2007

History

• Accepted
  23 Mar 2007
• Received
  19 May 2006