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Cardiovascular Effects of Nondepolarizing Relaxants Employed for Pretreatment Prior Bruce P

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Cardiovascular Effects of Nondepolarizing Relaxants Employed for Pretreatment Prior Bruce P 13 Cardiovascular effects of nondepolarizing relaxants employed for pretreatment prior Bruce P. Kingsley Me, M. Sue Vaughan, vHt), Robert W~ Vaughan MD to succinylcholine A pregnant woman with severe pre-eclampsia experi- Subparalyzing, pretreatment doses of nondepolar- enced a hypertensive crisis following a pretreatment dose izing muscle relaxants are widely employed in the (20 rag) of gallamine. That episode initiated a study to induction period to limit the adverse effects of determine the cardiovascular effects of non-depolarizing succinylcholine. These modest doses of nonde- muscle relaxants in 58 nonobese, ASA physical status polarizing muscle relaxants can limit changes in I and I1 adults. Subjects were assigned randomly to intragastric ~'z and intraocular pressures, 3 serum one of five treatment groups as follows: gallamine potassium, 4 creatine kinase, 5 the incidence of (0.29 mg-kg J), d-tuboeurarine (0~04 mg-kg t ), meto- postoperative myalgias,6 and the bradycardia asso- curine (0.014 mg.kg-J ), pancuronium (0.007 mg'kg-t ), ciated with a repeat dose of succinylcholine. 7'8 or normal saline (control). Baseline measurements of Although controversial and recently challenged, 9 systolic, diastolic, mean arterial pressure, heart rate "pretreatment" has become an accepted part of the (HR) and rate pressure product (calculated RPP) were rapid induction-intubation sequence for general recorded at one-minute intervals while electrocardio- anaesthesia, particularly for the patient with a full gram, lead H, was recorded continuously. Statistically stomach, ao significant increases occurred in HR at minutes 2, 3 and 4; RPP at minutes 3 and4; and per cent change in HR at Case Summary minutes 2, 3 and 4 foUowing gallamine pretreatment. The A 38-year-old primagravida at 30 weeks' gestation rise in RPP was predominately due to the elevation in required emergency Cesarean section for severe HR. These results suggest that even modest doses of pre-eclampsia complicated by progressive reduc- gallamine should be avoided in clinical situations where tion in platelet count. There was no history of lability el cardiovascular dynamics can be anticipated. previous anaesthetics, major illnesses, or adverse reactions to medications. The patient had been Key words taking alpha-methyl dopa and hydrochlorthiazide NEUROMUSCULAR BLOCKING DRUGS: d-tubo- for blood pressure control. Physical examination curarine, gallamine, metocurine, pancuronium, revealed: weight, 66kg; blood pressure, 220/110 suecinylcholine. ton'; pulse, 84 beats/minute; temperature, 37.0 ~ C orally; respiration, 16 per minute. The upper airway and the cardiopulmonary system were judged nor- mal. Pitting edema (2+/4+) of the lower extremi- From the Department of Anesthesiology, Arizona ties and sustained ankle clonus were demonstrated. Health Sciences Center, Tucson, Arizona. Laboratory results were: haemoglobin 15.6 gm/dl, Address correspondence to: R.W. Vaughan ~, serum potassium 4.1 mEqtL, blood urea nitrogen Department of Anesthesiology, University of North 28 mg/dl, serum creatinine 1.3 mg/dl, and a normal Carolina School of Medicine, Chapel Hill, N.C. 27514. coagulation profile with the single exception of a CAN ANAESTH SOC J 1984 / 31: I / pp13-19 14 CANADIAN ANAESTHETISTS' SOCIETY JOURNAL platelet count of 17,000/mm 3. No urine was obtain- ment doses have been presumed to be innocuous. able for analysis. However, their effects have not been examined The patient was placed in a quiet room with within a controlled experimental (control group, subdued lighting. Using local anaesthesia, a periph- randomization, double blinded) design. The impor- eral intravenous cannula was inserted, a loading tance of considering the cardiovascular effects of dose of magnesium sulfate (4 Gm) administered and these small doses was the subject of a recent a continuous infusion initiated. Using local anaes- editorial. ]2 To evaluate this question we performed thesia, a teflon 20 gauge 1J''e cannula was inserted a prospective, randomized, blinded clinical trial. into the left radial artery at the wrist and attached to a pressure transducer. Using the same technique, a Methods central venous cannula was inserted via the left Following protocol approval by the institutional anteeubital vein. Initial readings were a blood Human Subjects Committee, vebal and written pressure of220/110 tort and central venous pressure consent was obtained from 58 subjects on the (CVP) of -5 tort. Rapid hydration was begun until evening prior to operation, ASA physical status 1 the CVP approached normal levels. The patient was and I1 patients scheduled for elective surgical taken to the operating room where her blood procedures udder genera] anaesthesia were chosen pressure was controlled (160/80 ton-) with sodium for study. Subjects excluded from the clinical trial nitroprusside (1 Izg-kg-t.min-I). Subsequently were those who were obese (body mass index > anaesthetic induction was begun. After the patient 30kg/m2), ~3 allergic to iodine or bromide, or received oxygen by mask for five minutes, galla- receiving adrenergic blocking drugs. All patients mine (20rag) was given into the peripheral intra- were fasted after midnight and no patient received venous infusion. The pulse rate immediately in- overnight intravenous hydration. Both preoperative creased from 90 to 130 and the blood pressure medications and preoxygenation were withheld. increased from 160/95 to 230/115. This hyper- Patients were assigned, using a table of random tensive response was unchanged by increasing numbers, to one of five pretreatment groups as the nitroprusside infusion to approximately 4 ~,g. follows: gaUamine (0.29 mg'kg-~), d-tubocurarine kg-Lmin -l. Anaesthetic induction proceeded with (0.04 mg.kg- 1), metocurine (0.014 mg.kg- l), pan- sodium thiopentone (200 mg) while skeletal muscle curonium (0.007 mg'kg-l), or normal saline (con- relaxation was acomplished with succinylcholine trol). The total volume of the pretreatment agent (100rag). When the lash reflex was lost following was adjusted to one ml prior to injection. thiopental, cricoid pressure was applied and the Upon arrival in the operating room holding area, larynx was intubated with a cuffed endotracheal an intravenous cannula was placed and the patient tube. Following induction and intubation, the blood transported to the operating suite where blood pressure decreased to 200/90. Six minutes after pressure (BP), electrocardiogram (EKG), and chest induction of anaesthesia a viable infant was de- stethoscope monitors were applied. An automated livered, the placenta manually removed, and the oscillometric technique (Sentry) was employed to nitroprusside infusmn discontinued. The BP slowly measure systolic (SBP), diastolic (DBP), and heart decreased to 100/60. The remainder of the case was rate (HR) as well as calculate mean arterial pressure uneventful. The mother and child were followed for (MAP). Subsequent calculations included rate pres- 48 hours and no sequelae were observed. sure product (HR times SBP) and per cent change from baseline of HR and RPP. Lead I1 of the EKG Comment was recorded continuously. Tile cardiovascular and autonomic side effects of All cardiovascular measurements were recorded paralyzing doses of nondepolarizing neuromuscular by a knowledgeable, blinded clinical investigator blockers have been extensively examined. For (MSV). The same anaesthesiologist (RWV) admin- example, in anaesthetized patients, paralyzing istered all pretreatment drugs and induction agents. doses of gaUamine result in increases in heart rate The other investigator (BPK), blinded to patient and cardiac output secondary to the muscarinic variables and assigned pretreatment group, evalu- blocking, chronotropic actions of the drug. lj The ated all EKG recordings for presence and tinting of cardiovascular effects of these drugs in pretreat- dysrhythmias. Kingsley et al.: CARDIOVASCULAR EFFECTS OF PRETREATMENT RELAXANTS 15 TABLE I Descriptivecharacteristics of the sample by treatmentgroup" (mean • SE) Gallarninef DTC MTC PCB NS Number of patients 10 l 3 12 12 11 Age (yrs) 39+5 32---3 41 ---5 38-+'4 ,15• Weight (kg) 71• 59---3 63• 69---3 68---5 Height (cm) ]67--.5 162-+2 165• 168--.2 166+3 *p > 0.05 among groups. "tAbbreviatioes: DTC = d-tubocurarine, MTC = metocurine, PCB = pancuronium, NS = normal ~aline. laryngoscopy. Measurement of cardiovascular vari- Blood Pressure ables at minute six concluded the study. Gallamine Results were analyzed using a one-way analysis 170- DTC MTC of variance and the TukeyrB multiple range test for 1604 PCB o 1504 ~---o Oonlrol ,,'" interpretation of differences among groups. In 3-- addition, Chi-square analysis was used to test dif- ferences among groups for incidence of dysrhyth- 120- mias. Statistical significance was set at p --< 0.05. 110- I00- Results o 90- Fifty-eight adult subjects, 12 males and 46 females, ...... were studied. Descriptive characteristics for the 70- total sample included (mean --- SE (range)): age, 39 - 2 years (19-84); weight, 66 +-- 2kg (41-127); 0 1 2 3 4 $ 6 and height, 165 --- 1.3 cm (147 201). There was no difference among the pretreatment groups with respect to age, weight, height (Table I), medication Time (minutes) history, allergies, or smoking history. Of the 35 patients requiring intubation, eight were intubated FIGURE I Systolic and diastolie blood pressurein pretreat- just prior to minute six and 27 were intubated after ment groups and control. No significantdifference occurred among groups at any time interval
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