Katsuakira Kono

The use of H1 and H2 histamine antagonists with morphine anesthesia: a double-blind study.

High doses of morphine can produce significant cardiovascular effects generally attributed to histamine release. The authors examined the possibility that H1 and H2 histamine antagonists might prove beneficial in preventing these responses. In a randomized double-blind study, four groups of 10 patients each received 1 mg/kg morphine and either a placebo, diphenhydramine (H1), cimetidine (H2), or both of the histamine antagonists. The morphine-placebo group demonstrated a marked elevation in plasma histamine levels (880 ± 163 to 7437 ± 2684 pg/ml), a decrease in systemic vascular resistance (SVR) (15.5 to 9.0 l torr/(1 ± min−1) and diastolic BP (71 ± 3 to 45 ± 4 torr) and an increase in cardiac index (CI) (2.4 ± 0.2 to 3.0 ± 0.21·min−1·m−2). The administration of either cimetidine or diphenhydramine with morphine provided minimal protection. Those patients who received morphine and both antagonists demonstrated significant attenuation of these responses (CI 2.5 ± 0.2 to 2.5 ± 0.1 1·min−1·m−2; SVR 17.4 to 14.6 torr/(1·min−1) although plasma histamine levels showed a comparable increase (1059 ± 222 to 7653 ± 4242 pg/ml). These data demonstrate directly that many of the hemodynamic effects of morphine can be attributed to histamine release. They further demonstrate that significant hemodynamic protection can be obtained by the use of histamine antagonists and the combination of H1 and H2 antagonists is superior to either given alone.

Attenuation of the stress response to cardiopulmonary bypass by the addition of pulsatile flow.

The effect of pulsatile flow during cardiopulmonary bypass on the hormonal stress response was studied in 26 patients. Thirteen had routine bypass and 13 had pulsatile bypass with an average pulse pressure of 30 mm Hg. Plasma vasopressin levels were significantly elevated during bypass in both groups, but were lower with pulsation (66 ± 11 vs 36.3 pg/ml, p < 0.05). Epinephrine levels increased in both groups during bypass, but were higher after bypass (1179 ± 448 vs 713 ± 140 pg/ml, p < 0.05) and in the recovery room (1428 ± 428 vs 699 ± 155 pg/ml, p < 0.05) in the nonpulsatile group. The same response was noted in the norepinephrine levels (924 ± 225 vs 465 ± 90 pg/ml, p < 0.05; 1915 ± 491 vs 717 ± 112 pg/ml, p < 0.05). There were no significant changes in renin activity in either group, but the increase after cardiopulmonary bypass was greater in the nonpulsatile group (2.0 ± 0.7 vs 1.36 ± 0.4 ng/mI/hr, NS). These data suggest that pulsatile flow significantly attenuates the vasopressin and catecholamine stress response to cardiopulmonary bypass. This may explain the increased flow requirements and better tissue perfusion and organ function and the decreased incidence of postoperative hypertension after bypass using pulsatile flow.

Plasma Vasopressin Levels and Urinary Sodium Excretion during Cardiopulmonary Bypass with and without Pulsatile Flow

The use of pulsatile perfusion during bypass should create a more physiological milieu and thus attenuate the vasopressin stress response. To determine this, 20 patients scheduled for elective coronary artery bypass operation were studied in two groups. Group 1 had a standard nonpulsatile perfusion, and in Group 2 a pulsatile pump was used. Measurements were made before and after anesthesia, after surgical incision, and at 15 and 30 minutes during and after cardiopulmonary bypass. In both groups, vasopressin levels were significantly elevated after sternotomy (4.5 +/- 1.5 to 37 +/- 10 pg/ml in Group 1 and 3.1 +/- 1.2 to 33 +/- 9 pg/ml in Group 2, p less than 0.05) and during bypass (198 +/- 19 pg/ml in Group 1 and 113 +/- 16 pg/ml in Group 2) but were higher in Group 1 (p less than 0.05). With comparable perfusion pressures in both groups, Group 2 required higher flow (4.2 +/- 0.2 versus 3.5 +/- 0.3 L/min, p less than 0.05) and had lower resistance (1,351 +/- 182 versus 1,841 +/- 229 dynes sec cm-5, p less than 0.05) and higher urine Na+ (123 +/- 5 versus 101 +/- 8 mEq/L, p less than 0.05). These data demonstrate that pulsatile flow can significantly attentuate the vasopressin stress response to bypass. Since vasopressin, at these concentrations, is a potent vasoconstrictor and is capable of producing a Na+ diuresis, this may partially explain the higher flow requirements and the decrease in Na+ excretion.

Renal function and stress response during halothane or fentanyl anesthesia.

The effects of anesthesia on hormonal stress response and renal function were measured before institution of cardiopulmonary bypass in two groups of patients undergoing elective coronary artery surgery. Group 1 (10 patients) received fentanyl, 100 μg/kg, and N2O/O2; group 2 (12 patients) received halothane and N2O/O2. Patients in group 1 showed no significant changes in plasma levels of vasopressin, renin, or aldosterone during anesthesia or operation. This same group, however, demonstrated significant decreases in plasma levels of cortisol (8.4 ± 1 to 4.2 ± 1 μg%, p < 0.01), epinephrine (260 ± 72 to 97 ± 28 pg/ml, p < 0.05), and norepinephrine (715 ± 177 to 322 ± 46 pg/ml, p < 0.05) during operation. This was accompanied by an increase in urine volume (2.1 ± 0.8 to 7.6 ± 2 ml/min, p < 0.05), a decrease in urine osmolality (610 ± 82 to 166 ± 60 mOsm/kg, p < 0.01), and urine Na+ (54 ± 12 to 16 ± 4 meq/L, p < 0.01) and no change in creatinine clearance. In contrast, in the group 2 patients during operation plasma levels of cortisol (11.7 ± 2 to 31.1 ± 2 μg%, p < 0.01), aldosterone (60 ± 14 to 106 ± 2 pg/ml, p < 0.01), and vasopressin (10.4 ± 1 to 23.3 ± 3 pg/ml, p < 0.01) all increased. This was accompanied by a significant decrease in creatinine clearance (148 ± 52 to 92 ± 12 ml/min/m2, p < 0.05). The data demonstrate that high dose fentanyl anesthesia can significantly attenuate the hormonal stress response to operation and preserve renal function. They also suggest that decreases in renal function observed with anesthesia and operation may be a reflection of the hormonal changes associated with surgical stimulation.

Variations in hemodynamic and stress hormonal responses in open heart surgery with buprenorphine/diazepam anesthesia

The use of buprenorphine-diazepam-N2O (60%)-O2 anesthesia in open heart surgery was investigated. The authors examined the hemodynamic changes produced and the response of stress hormones. Twenty adult patients with atrial septal defects undergoing surgical correction were studied in two groups of 10, receiving either 6 micrograms/kg of buprenorphine (B6) or 12 micrograms/kg of buprenorphine (B12) for the induction of anesthesia. Both groups received a subsequent dose of 6 micrograms/kg of buprenorphine with the commencement of extracorporeal circulation (ECC). With surgery, mean arterial pressure showed a transient increase in both groups and thereafter was stable. Heart rate in the B6 group was increased from the onset of surgery to the day after, while the B12 group showed no significant change. Filling pressures showed no change in either group. Plasma catecholamine concentrations in the B6 group, in contrast to the B12 group, increased significantly from midoperation to after completion of the operation (ECC 10 minutes, B6 group v B12 group: plasma norepinephrine 616 +/- 231 v 195 +/- 38 pg/mL, plasma epinephrine 1385 +/- 392 v 572 +/- 132 pg/mL, P less than 0.05). Plasma ADH levels in both groups rose with the commencement of surgery, reaching a peak at ECC 10 minutes (B6 group 88.1 +/- 8.4 v B12 group 124.4 +/- 27.2 pg/mL). However, in contrast to plasma catecholamines, the antidiuretic hormone (ADH) levels in the B12 group remained higher until the first postoperative day. Therefore, patients who received the larger dose of buprenorphine had better control of hemodynamics and catecholamines, but a greater elevation of plasma ADH levels.

Effects of diltiazem on renin-aldosterone and ACTH-adrenocortical function during upper abdominal surgery

STUDY OBJECTIVE To observe the effects of continuous intravenous infusion of diltiazem on the renin-aldosterone system and ACTH-adrenocortical axis responses during surgical stimulation. DESIGN Randomized study of intravenous diltiazem. SETTING Operating room at the Hyogo Medical College Hospital. PATIENTS Twenty-three patients undergoing upper abdominal surgery were divided into two groups: the control group (n = 10) and the diltiazem group (n = 13). All the patients were without any complications and classified as ASA physical status I. INTERVENTIONS Patients in the diltiazem group received an infusion of 10 micrograms/kg/min for 90 to 120 minutes following skin incision. MEASUREMENTS AND MAIN RESULTS Plasma adrenocorticotropic hormone, plasma aldosterone and cortisol concentrations, and plasma renin activity were determined with radioimmunoassay before the induction of anesthesia at 10, 30, 60, and 90 minutes after skin incision and at the end of anesthesia. Renin activity did not change significantly. Maximal increases in plasma adrenocorticotropic hormone, aldosterone, and cortisol observed 90 minutes after skin incision were 355 +/- 95 pg/ml, 118 +/- 30 pg/ml, and 14.2 +/- 2.3 micrograms/dl in the control group versus 246 +/- 41 pg/ml, 119 +/- 25 pg/ml, and 15.0 +/- 1.8 micrograms/dl in the diltiazem group, respectively, and there were no significant differences between these groups. Adrenocorticotropic hormone was significantly lower in the diltiazem group compared with that in the control group 60 minutes after the start of surgery (p less than 0.05). There was marked natriuresis (40 +/- 25 microEq/min vs 470 +/- 147 microEq/min at the 90-minute mark) and diuresis (0.16 +/- 0.13 ml/min vs 2.53 +/- 0.88 ml/min) in the diltiazem group. CONCLUSIONS Diltiazem at this dose increased urine output and sodium excretion without affecting most of these hormonal responses to surgical stimulation. These findings suggest that diltiazem has beneficial renal effects independent of hormonal concentrations.