BJA Advance Access originally published online on August 16, 2006
British Journal of Anaesthesia 2006 97(5):654-657; doi:10.1093/bja/ael221
General anaesthesia for the cocaine abusing patient. Is it safe?
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard, Dallas, TX 75390-9068, USA
*Corresponding author. E-mail: gary.hill{at}utsouthwestern.edu
Accepted for publication July 3, 2006.
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Abstract |
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Background. Commonly, cocaine abusing patient are scheduled for elective surgery with a positive urine test for cocaine metabolites. As many of these patients were clinically non-toxic [normal arterial pressure and heart rate, normothermic, and a normal (or unchanged from previous) ECG, including a QTc interval <500 ms], we have recently proceeded with elective surgery requiring general anaesthesia in this patient group.
Methods. Forty urine cocaine positive patients were compared with an equal number of drug-free controls in a prospective, non-randomized, blinded analysis. Intraoperative mean arterial blood pressure, ST segment analysis, heart rate and body temperature were recorded and compared.
Results. Cardiovascular stability during and after general anaesthesia in cocaine positive, non-toxic patients was not significantly different when compared with an age and ASA matched drug-free control group.
Conclusions. These results demonstrate that the non-toxic cocaine abusing patient can be administered general anaesthesia with no greater risk than comparable age and ASA matched drug-free patients.
Keywords: anaesthesia, general; anaesthetics local, cocaine; complications, adverse events; QTc interval
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Introduction |
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Previous investigators found 38% of major trauma victims and 57% of victims of violent assault tested positive for cocaine abuse after presentation for treatment at a large urban trauma centre.1 We have similarly noticed a high rate (estimated at 0.5–1% of the total surgical case volume) of cocaine abuse (demonstrated by a positive urine test for cocaine metabolites) in patients presenting for elective same day surgery similarly located in a major teaching hospital in a large urban setting. Because of the increased costs and resource wastage associated with the routine cancellation of such patients, we have recently proceeded with elective surgery requiring general anaesthesia in the urine positive, non-toxic cocaine abusing patient. As no peer-reviewed report has been previously published concerning this increasingly common clinical scenario, we undertook a medical record-based analysis in order to evaluate the outcomes of general anaesthesia in this patient population.
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Methods |
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After local institutional review board approval (requirement for patient informed consent was waived), a prospective non-randomized blinded study of 40 patients was undertaken. The following criteria were used for inclusion in the study population: an adult (18–55 yr of age) presenting for elective surgery requiring general anaesthesia with a positive urine test for cocaine metabolites. No indication of acute cocaine toxicity [normal or unchanged from a previous ECG including an automated Bazett-formula determined heart rate corrected QT interval (QTc) of less than 500 ms,2 normal body temperature, systolic, diastolic and mean non-invasively determined arterial blood pressures and heart rate more or less than 10% of previously recorded values during a clinic visit in which the patient tested negative for urinary cocaine metabolites, if available, or vital signs within generally accepted norms] was required before proceeding with general anaesthesia.
Standard monitors routinely used for general anaesthesia [peripheral venous access, temperature monitoring, two-lead ECG (lead II and precordial lead V5 with automated ST segment analysis), non-invasive arterial pressure cuff, finger pulse oximeter and end-tidal gas (carbon dioxide and sevoflurane) analysis] (S/5 Anesthesia Monitor, GE Healthcare, Helsinki, Finland) were applied. After i.v. midazolam 0.02–0.03 mg kg–1 sedation, a standard general anaesthesia protocol was followed for all patients and included induction with propofol 1.5–2.0 mg kg–1 and maintained with fentanyl 1–5 µg kg–1, sevoflurane in N2O 50% in oxygen and vecuronium for neuromuscular block, if needed. Reversal of neuromuscular block was accomplished, if needed, by neostigmine, 40–70 µg kg–1, and glycopyrrolate, 3–6 µg kg–1, and adequacy of reversal was judged by the return of train-of-four stimulation to over 0.75 or a 5 s head lift.
The following information was gathered from the preoperative evaluation record: age, sex, height and weight, ASA physical status, ECG interpretation with QTc interval length, and systolic, diastolic and mean arterial blood pressures (MABP). From the manually recorded anaesthetic record: non-invasively determined systolic, diastolic, and MABP pressures measured, at the minimum, every 5 min, heart rate, body temperature, volume of crystalloid fluid administered, the number of episodes of ST segment elevation or depression >1 mm, end-tidal concentrations of sevoflurane, duration of anaesthesia (min) and the total dosage (µg) of fentanyl administered. From the postoperative recovery room record: length of stay, occurrence of arrhythmias, arterial blood pressure, heart rate and rhythm and body temperature, and the presence of any excitement or delirium during recovery. All patients in both groups received a 24 h post-surgery telephone interview from a member of the day surgery nursing team. The cocaine positive group was compared with an ASA physical status, surgical procedure and age-matched control group of equal number whose procedure occurred over approximately the same time interval (more or less than 3–4 months) using a similar anaesthetic technique.
The number of distinct cardiovascular episodes during general anaesthesia was determined for each patient. A distinct cardiovascular episode was defined as more or less than 30% change in heart rate or more or less than 40% change in MABP3 when compared with each patient's preanaesthetic induction baseline values. A research assistant blinded as to which group each patient belonged determined the number of distinct cardiovascular episodes from the anaesthetic record for all patients from both groups. The protocol determined that these distinct cardiovascular episodes were not to be treated with vasoactive drug therapy unless the above definitions were met. The number of cardiovascular episodes requiring vasoactive drug administration (either vasopressor, usually phenylephrine, or vasodilator, usually labetalol) was recorded. The end-tidal concentration of sevoflurane required for each subject was determined by calculating the mean concentration throughout the surgical procedure averaged over 15 min time intervals. The total number of distinct cardiovascular episodes was recorded in each group. The unpaired Student's t-test or the Fisher's exact test was used to compare the cocaine group against the control group on all measured variables. P-values of 0.05 or less defined significance.
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Results |
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The most frequent surgical procedure in both groups was an orthopaedic procedure (open reduction and internal fixation of bone fractures or orthopaedic hardware removal), the remainder being a mix of cases, including laparoscopic cholecystectomy (two in each group) and rectal/anal procedures. The largest individual estimated blood loss was approximately 150 ml, while the majority of procedures in both groups reported estimated blood loss of less than approximately 100 ml. While the control group had significantly greater age (P=0.01) and body weight (P=0.02), no other significant differences were found in patient characteristics between groups in any other recorded variables, including the preoperative ECG determined automated QTc interval (Table 1). Recorded mean (SD) end-tidal sevoflurane concentrations, volume (ml h–1) of infused crystalloids, distinct episodes of ST segment elevation or depression >1 mm, duration of post-anaesthesia recovery room stay (min), intraoperative body temperature, total fentanyl dose (µg) and duration of anaesthesia (min) were not significantly different between groups (Table 2). Intraoperatively, the cocaine group had a total of three distinct cardiovascular episodes and the control group had a total of four distinct episodes (all episodes –40% MABP, P-value=0.28) (Table 3). Vasoactive drug use (phenylephrine in each episode) was required on three occasions in the cocaine group and three occasions in the control group (P-value=1.0). No labetalol treatment was required in either group. No (0) distinct episodes of more or less than 30% change in heart rate (when compared with baseline values) was noted in either group. No intraoperative or postoperative arrhythmia was noted in either group. No patient in either group reported significant surgical or anaesthetic complications during the 24 h post-surgery follow-up telephone interview.
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Discussion |
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The physiologic effects of cocaine ingestion are shortlasting. The chronotropic effect of i.v. cocaine peaks at 5–15 min while the half-life of this effect is 23.6 min.4 After intranasal ingestion, peak plasma cocaine concentrations are found at 15–60 min (paralleling the peak cardiovascular effects), with an elimination half-life of 45–90 min.5 While the physiologic effects of cocaine ingestion are complex and includes inhibition of the norepinephrine, dopamine and serotonin transporter mechanisms,6 it is generally agreed that the physiologic effects of ingested cocaine parallel the increase of plasma levels of norepinephrine.7 This increase in norepinephrine is considered to be secondary to the inhibition of the active reuptake of endogenously released norepinephrine at adrenergic nerve fibres.8 Thus, the increase in systolic, diastolic and mean arterial blood pressure, heart rate, body temperature and the potential for coronary artery vasospasm resulting in ischaemia-induced cardiac arrythmias are considered to be caused by a sympathetic stimulation syndrome secondary to increased plasma levels of norepinephrine.9
Ingested cocaine is rapidly hydrolysed, primarily by plasma (pseudocholinesterase) and liver esterases,9 10 to ecgonine methyl ester (EME) and benzoylecgonine. These metabolites possess no cocaine-like stimulation effects, detected in urine by gas or liquid chromatography, and are responsible for positive urine testing after cocaine ingestion. Because the biological half-lives of EME and benzoylecgonine are much longer than that of cocaine (6 and 8 h, respectively, compared with 30–90 min for cocaine),5 7 9 10 these metabolites can be detected in urine for as long as 60 h9 and up to 10 days11 after cocaine ingestion. Therefore, the cocaine abuser may present with a positive urine test for cocaine metabolites but with normal physiologic variables, including normal arterial pressure, body temperature, heart rate, electrocardiogram and emotional behaviour. As our institution is located in a major metropolitan area with a patient population who frequently test positive for illegal street drug use, this clinical presentation is increasingly seen in our patients scheduled for elective surgery.
While the safety of general anaesthesia in the toxic cocaine abuser (after recent ingestion) is not well reported, general anaesthesia in this group of patients is generally considered to have increased risk, particularly if ketamine (a reuptake inhibitor of endogenously released norepinephrine12) is included in the anaesthetic technique.13 Clinical studies of the relationship between anaesthesia and cocaine intoxication after recent ingestion are largely limited to the obstetric population and further limited to studies evaluating the relationship between maternal cocaine abuse and adverse outcomes for the fetus and newborn.14 No previous peer-reviewed publication has evaluated the risks of elective surgery requiring general anaesthesia for the non-toxic, urine positive cocaine abuser.
A major concern in the clinical anaesthetic management of the cocaine abusing patient is the appearance of cardiac arrhythmias, such as ventricular tachycardia, frequent premature ventricular beats or torsades de pointes.15 While the mechanism for the induction of these arrhythmias had previously been considered to be secondary to coronary artery vasospasm resulting in myocardial ischaemia, cocaine-induced sodium and potassium channel blockade is currently thought to be more important.15–18 Cocaine-induced cation channel blockade causes lengthening of the QTc interval by prolongation of the action potential duration,15 16 an effect similar to that caused by the Vaughn–Williams antiarrhythmic class 1c drug flecainide. This sodium and potassium channel blockade results in QRS and QTc prolongation which is considered to be the primary underlying mechanism for the induction of these cocaine-induced arrhythmias,15 17 especially the torsades de pointes type of polymorphic ventricular tachycardia. In support of this concept, Beckman and colleagues18 demonstrated that the administration of a concentrated solution of sodium ions (sodium bicarbonate) will effectively antagonize the intracardiac conduction slowing (QRS and QTc prolongation) caused by cocaine-induced sodium channel blockade, thereby effectively treating ventricular arrhythmias. The mechanism for the improvement of cocaine-induced intracardiac conduction slowing18 by sodium ion administration is pharmacologically similar in concept to the reversal of calcium channel blocker toxicity with ionized calcium.19 Our failure to observe any arrhythmia occurrence in the cocaine group may be partly explained by the protocol requirement of an automated QTc interval duration of less than 500 ms before proceeding with general anaesthesia. Therefore, the results of this report may not apply to the cocaine abusing patient with prolongation of this electrocardiographically determined interval.
While all patients in both groups were ASA class I–II, the mean age of the control group was significantly greater than the cocaine positive group. Departmental guidelines omitting the requirement of routine preoperative ECG (and subsequent QTc interval determination) for patients under 60 yr of age created difficulty in finding qualified younger control group candidates. Because other investigators3 report the incidence of similarly defined hypotensive episodes equal to that found in our control group, we feel confident the control group is a valid representation of patients scheduled for elective surgery requiring general anaesthesia.
Finally, a prolonged QTc interval has been defined as greater than 450 ms in women and 440 ms in men,20 and while other investigators21 demonstrated a QTc of over 440 ms significantly increased the risk of fatal ventricular arrhythmias, our protocol determined that general anaesthesia could be administered if the QTc interval did not exceed 500 ms. The use of a 500 ms cut-off was based on peer-reviewed reports that the induction of ventricular arrythmias occurring during electrolyte disturbance (hypokalaemia)22 and non-cardiac drug ingestion (including psychotherapeutic drugs, such as amitriptyline, lithium and chlorpromazine)23 required a QTc interval exceeding 500 ms. Therefore, a QTc interval of less than 500 ms was required before proceeding with elective surgery requiring general anaesthesia.
In summary, these results demonstrate that humans presenting for elective surgery requiring general anaesthesia who test urine positive for cocaine but are clinically non-toxic are at no greater risk than drug-free patients. Routine cancellation of these patients is unwarranted and wasteful of medical resources. The authors caution that these results may not be applicable to the cocaine abusing patient with an automated QTc interval of 500 ms or greater on the preoperative electrocardiogram or to those patients whose vital signs indicate acute cocaine intoxication.
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