Antipsychotic drugs used in the treatment of schizophrenia have been associated with a range of potentially serious side-effects. The antipsychotics might interact with anaesthetics or affect the patient's postoperative condition. The preoperative use of antipsychotics makes patients more susceptible to the hypotensive action of general anaesthesia. Approximately 20% of schizophrenic patients taking antipsychotic medications have episodes of profound hypotension after the induction of anaesthesia . Molnar and Fava  suggested that surgical stress worsens the psychotic symptoms in schizophrenic patients. It was reported that chronic schizophrenic patients had a high rate of postoperative confusion . Thus, preoperative discontinuation of antipsychotic drugs may increase episodes of psychotic symptoms, e.g. hallucinations and agitation in the perioperative course. However, there is little published information describing the effects of discontinuation of antipsychotics before surgery on perioperative outcome. Postoperative complications of schizophrenic patients who continued or discontinued antipsychotics before surgery were therefore compared.
The study was approved by the Medical Ethics Committee of our institution. Informed consent was obtained from all patients and their families. The study was a prospective randomized trial. A total of 101 patients, aged 40-60 yr, who were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III)  criteria by psychiatrists were studied. All patients were undergoing minor surgery under anaesthesia, which included orthopaedic procedures (surgical correction of bone fractures and surgery on the lumbar spinal) in 56 patients, inguinal herniorrhaphy in 16 patients, transurethral prostatectomy in 18 patients and operation on the anus in 11 patients. The patients were randomly divided into two groups: 49 patients in Group 1 continued antipsychotic drugs before surgery and 52 patients in Group 2 discontinued antipsychotic drugs 72 h before surgery. Randomization was performed by computer-generated codes. Patients with a history of cardiovascular disease and alcohol abuse were excluded. Anaesthesia was induced with fentanyl 2 μg kg−1 and propofol 1.5 mg kg−1 intravenously and endotracheal intubation was facilitated by vecuronium 0.1 mg kg−1 intravenously. Anaesthesia was maintained with sevoflurane 1.2-2.0% inspired and adjusted according to clinical signs such as increases in heart rate and arterial pressure. All patients received fentanyl 6 μg kg−1 before skin incision followed by further increments when needed. Postoperatively, all patients were given a diclofenac 50 mg suppository every 6 h. Pentazocine was given if further pain occurred. Postoperative confusion was diagnosed by psychiatrists using DSM-III and the confusion assessment method (CAM), which has been shown to be a sensitive and reliable method for assessment of confusion . Patients were examined at least once daily with CAM until the 10th day postoperation, and the assessment of confusion was performed whenever a patient was judged by the nursing staff to be changed mentally. Haloperidol 5 mg was administered to treat postoperative confusion. In this study, all patients received the standard interview for the Positive and Negative Syndrome Scale (PANSS)  to evaluate the pre- and postoperative psychiatric state at 2 days before and the fourth day postoperation. Pain scores were evaluated by nurses every 8 h for the first 24 h and every 24 h thereafter. Pain was estimated using a 100 mm visual analogue scale (VAS) (0 mm = no pain, 100 mm = worst imaginable pain). The study was blinded for both psychiatrists and nurses. Data are expressed as mean ± standard deviation. Comparisons between groups in VAS pain score, blood pressure, heart rate, mean duration of anaesthesia and surgery, and mean volume of blood loss were analysed by repeated measures of ANOVA using Bonferroni's correction. Comparison in PANSS scores pre- and postoperation was analysed by ANOVA followed by a Dunnett's test. P < 0.05 was considered significant. TABLE
Postoperative confusion during the first 4 days occurred in seven (14%) of 49 patients in Group 1 and in 16 (31%) of 52 patients in Group 2. The incidence rate of confusion in Group 1 was significantly (P = 0.048) lower than that of Group 2. The mean consumption of haloperidol was 5.6 ± 2.2 mg in Group 1, which was significantly lower than the 13.2 ± 6.7 mg in Group 2. Serious confusion, such as hallucinations or paranoid delusions, was observed in one patient in Group 1 and in six patients in Group 2. There was no relationship between age and postoperative confusion. Mean positive, negative and general PANSS score in both groups did not change pre- and postoperation. Eight (16%) patients of 49 in Group 1 and seven (13%) patients of 52 in Group 2 had episodes of hypotension with systolic pressure <70 mmHg 2 min after the induction. There were no haemodynamic differences in mean systolic, diastolic pressure and heart rate before induction, 2 min after induction, 5 min after endotracheal intubation and 5 min after skin incision between the two groups. Three (6%) patients of 49 in Group 1 and four (8%) patients of 52 in Group 2 developed dysrhythmias. There were no clinically significant differences in the postoperative pain score between the two groups for 3 days postoperation.
It was shown that the incidence rate of postoperative confusion was significantly higher in schizophrenic patients if the antipsychotics were discontinued before surgery than in patients who continued taking their medication perioperatively. The biological effects of antipsychotic drugs, such as phenothiazines and butyrophenones, usually persist for at least 24 h, as the half-lives of antipsychotic drugs used in the study were 20-31 h for chlorpromazine, 8-12 h for perphenazine, 13-23 h for haloperidol and 20-31 h for bromperidol. The peak incidence of postoperative confusion was on the second day of operation in Group 1 and on the day of operation in Group 2. In this study, the antipsychotic agents were discontinued in Group 2 three days before surgery and were resumed 24 h after surgery. The patients in Group 1 received their antipsychotic medication until surgery and the administration was resumed 24 h later. The incidence rate of postoperative confusion 36 h after re-administration of the drugs was zero in both groups. Therefore, withdrawal symptoms resulting from discontinuation of antipsychotics appear to contribute to a cause of postoperative confusion in schizophrenic patients. The symptoms are known to be cholinergic-rebound, including sleep dysfunction, agitation, anxiety and restlessness. In addition, postoperative confusion among patients who discontinued antipsychotics was more severe than that of patients who continued antipsychotic therapy. Postoperative confusion in schizophrenic patients has been associated with adverse clinical and economic outcomes, including high rates of complications, poor functional recovery, increased length of stay and high costs . Schizophrenic patients sometimes touch wounds or remove infusion lines. It would therefore be beneficial both for the patient and for the care provider to reduce the incidence of postoperative confusion in schizophrenic patients. It is concluded that patients with chronic schizophrenia should continue their antipsychotic medication perioperatively.
Department of Anesthesiology; Hirosaki National Hospital; Hirosaki, Aomori, Japan
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