Urine and plasma catecholamine and cortisol concentrations after myocardial revascularization. Modulation by continuous sedation. Multicenter Study of Perioperative Ischemia (McSPI) Research Group, and the Ischemia Research and Education Foundation (IREF).

BACKGROUND: Cardiopulmonary bypass is associated with substantial release of catecholamines and cortisol for 12 or more h. A technique was assessed that may mitigate the responses with continuous 12-h postoperative sedation using propofol. METHODS: One hundred twenty-one patients having primary elective cardiopulmonary bypass graft (CABG) surgery were enrolled in a double-blind, randomized trial and anesthetized using a standardized sufentanil-midazolam regimen. When arriving at the intensive care unit (ICU), patients were randomly assigned to either group SC (standard care), in which intermittent bolus administration of midazolam and morphine were given as required to keep patients comfortable; or group CP (continuous propofol), in which 12 h of continuous postoperative infusion of propofol was titrated to keep patients deeply sedated. Serial perioperative measurements of plasma and urine cortisol, epinephrine, norepinephrine, and dopamine were obtained; heart rate and blood pressure were recorded continuously, and medication use, including requirements for opioids and vasoactive drugs, was recorded. Repeated-measures analysis was used to assess differences between study groups for plasma catecholamine and cortisol levels at each measurement time. RESULTS: In the control state-before the initiation of postoperative sedation in the ICU-no significant differences between study groups were observed for urine or plasma catecholamine or cortisol concentrations. During the ICU study period, for the first 6-8 h, significant differences were found between study groups SC and CP in plasma cortisol (SC = 28 +/- 15 mg/dl; CP = 19 +/- 12 mg/dl; estimated mean difference [EMD] = 9 mg/dl; P = 0.0004), plasma epinephrine (SC = 132 +/- 120 micrograms/ml; CP = 77 +/- 122 micrograms/ml; EMD = 69 micrograms/ml; P = 0.009), urine cortisol (SC = 216 +/- 313 micrograms/ml; CP = 93 +/- 129 micrograms/ml; EMD = 127 micrograms/ml; P = 0.007), urine dopamine (SC = 85 +/- 48 micrograms; CP = 52 +/- 43 micrograms; EMD = 32 micrograms; P = 0.002), urine epinephrine (SC = 7 +/- 8 micrograms; CP = 4 +/- 5 micrograms; EMD = 3 micrograms; P = 0.0009), and urine norepinephrine (SC = 24 +/- 14 mg; CP = 13 +/- 9 mg; EMD = 11 mg; P = 0.0004). Reductions in urine and plasma catecholamine and cortisol concentrations found for the CP group generally persisted during the 12-h propofol infusion period and then rapidly returned toward control (SC group) values after propofol was discontinued. Postoperative opioid use was reduced in the CP group (SC = 97%; CP = 49%; P = 0.001), as was the incidence of tachycardia (SC = 79%; CP = 60%; P = 0.04) and hypertension (SC = 58%; CP = 33%; P = 0.01), but the incidence of hypotension was increased (SC = 49%; CP = 81%; P = 0.001). CONCLUSIONS: Cardiopulmonary bypass graft surgery is associated with substantial increases in plasma and urine catecholamine and cortisol concentrations, which persist for 12 or more h. This hormonal response may be mitigated by a technique of intensive continuous 12-h postoperative sedation with propofol, which is associated with a decrease in tachycardia and hypertension and an increase in hypotension.

Cardiovascular responses during sedation after coronary revascularization. Incidence of myocardial ischemia and hemodynamic episodes with propofol versus midazolam. Institutions of the McSPI Research Group.

BACKGROUND: Propofol sedation offers advantages for titration and rapid emergence in the critically ill patient, but concern for adverse hemodynamic effects potentially limits its use in these patients. The current study compares the cardiovascular effects of sedation with propofol versus midazolam during the first 12 h after coronary revascularization. METHODS: Three hundred fifty-one patients undergoing coronary revascularization were anesthetized using a standardized sufentanil/midazolam regimen, and assigned randomly to 12 h of sedation with either propofol or midazolam while tracheally intubated. The incidence and characteristics of hemodynamic episodes, defined as heart rate less than 60 or greater than 100 beats/min or systolic blood pressure greater than 140 or less than 90 mmHg, were determined using data electronically recorded at 1-min intervals. The presence of myocardial ischemia was determined using continuous three-channel Holter electrocardiography (ECG) and of myocardial infarctions (MI) using 12-lead ECG (Q wave MI, Minnesota Code) or creatine kinase isoenzymes (CK-MB) analysis (non-Q wave MI, peak CK-MB > 70 ng/ml, or CK-MB > 70 IU/I). RESULTS: Ninety-three percent of patients in both treatment groups had at least one hemodynamic episode during the period of postoperative sedation. Propofol sedation resulted in a 17% lower incidence of tachycardia (58% vs. 70%, propofol vs. midazolam; P = 0.04), a 28% lower incidence of hypertension (39% vs. 54%; P = 0.02), and a greater incidence of hypotension (68% vs. 51%; P = 0.01). Despite these hemodynamic effects, the incidence of myocardial ischemia did not differ between treatment groups (12% propofol vs. 13% midazolam; P = 0.66), nor did its severity, as measured by ischemic minutes per hour monitored (8.7 +/- 5.8 vs. 6.2 +/- 4.6 min/h, propofol vs. midazolam; P = 0.19) or ischemic area under the curve (6.8 +/- 4.0 vs. 5.3 +/- 4.2; P = 0.37). The incidence of cardiac death (one per group), Q wave MI (propofol, n = 7; midazolam, n = 3; P = 0.27), or non Q wave MI (propofol, n = 16; midazolam, n = 18; P = 0.81) did not differ between treatment groups. CONCLUSIONS: Hemodynamic episodes occur frequently in the first 12 h after coronary revascularization. Compared with a standard sedation regimen (midazolam), propofol sedation appears to modulate postoperative hemodynamic responses by reducing the incidence and severity of tachycardia and hypertension and increasing the incidence of hypotension. Both sedation regimens appear similarly safe with respect to myocardial ischemia. These findings indicate that propofol infusion provides effective sedation without deleterious hemodynamic effects in patients recovering from cardiac surgery.