Cecil H. Coggins

Fentanyl-oxygen anaesthesia for coronary artery surgery: cardiovascular and antidiuretic hormone responses

SummaryThis study demonstrates that larges doses of fentanyl, as the sole anaesthetic with ventilation with oxygen, produces complete anaesthesia and minimal changes in cardiovascular dynamics in patients with coronary artery disease. It also indicates that high dose fentanyl anaesthesia blocks the increases in plasma anti-diuretic hormone and cardiovascular dynamics which are so common with morphine and other anaesthetic techniques during tracheal intubation and surgical stimulation in patients with coronary artery disease. Our findings suggest that fentanyl-oxygen anaesthesia is an attractive technique in patients with coronary artery disease.RésuméDans cette étude portant sur 14 malades opérés pour pontage aortocoronarien, les auteurs ont mesuré la réponse du système cardiovasculaire et de ľhormone antidiurétique à des doses anesthésiques de fentanyl (20-80 ug-kg-1); les observations ont été faites avant et pendant la stimulation chirurgicale et en cours de circulation extracorporelle.A ces doses de fentanyl, on observe une légère augmentation de la fréquence cardiaque et de la pression artérielle moyenne, mais sans modification du volume systolique, du débit cardiaque et de la résistance vasculaire périphérique. Le taux plasmatique de ľhormone antidiurétique n’est pas modifié de façon significative par le fentanyl, quels qu’en soient la dose, ľincubation, ou le stimulus chirurgical, quelle qu’en soit ľintensité; par contre, on note une augmentation significative de ľADH plasmatique au cours de la circulation extracorporelle.Cess données montrent que chez le porteur de maladie coronarienne, de fortes doses de fentanyl associées à de ľoxygène pur, produisent une anesthésie complète; on ne note que des effets mineurs sur la dynamique cardiovasculaire et la production ďhormone antidiurétique avant toute stimulation chirurgicale ou pendant celle-ci. Ces données inclinent à penser que la combinaison fentanyl-oxygène apparaît recommandable pour ľanesthésie du malade coronarien.

The modification of diet in renal disease study group

Abstract The Modification of Diet in Renal Disease Trial is a multicenter randomized clinical trial for men and women aged 18–70 years with chronic renal disease who are not on dialysis and who have not had a kidney transplant. Study participants are randomized in a 2 × 2 factorial design to diets containing different amounts of protein and phosphorus and to two levels of blood pressure control. The prescribed modifications differ depending on the level of a patients kidney function. The primary outcome variable to compare diet or blood pressure groups is each patients slope (or the change) in glomerular filtration rate with time. This paper describes the study design with particular emphasis on sample size determination. Special statistical analysis issues that arise with slope as the outcome are also discussed.

Antidiuretic and Growth Hormone Responses during Coronary Artery Surgery with Sufentanil-Oxygen and Alfentanil-Oxygen Anesthesia in Man

Antidiuretic hormone (ADH), growth hormone (GH), and cardiovascular responses to large (anesthetic) doses of alfentanil (1.2 ± 0.02 mg/kg) and oxygen and sufentanil (13.1 ± 0.4 μg/kg) and oxygen were measured before and during surgery (including cardiopulmonary bypass) and at the end of surgery in 29 patients undergoing coronary artery bypass surgery. The data demonstrate that alfentanil-O2 and sufentanil-O2 result in little change in cardiovascular dynamics throughout anesthesia and surgery, and also prevent changes in plasma levels of ADH and GH at all times during the study. Our findings contrast with previous studies with other anesthetics, including fentanyl, in which plasma levels of ADH and GH become markedly elevated during bypass. The results suggest that alfentanil and sufentanil may block hormonal stress responses to surgical stimulus better than fentanyl does. The clinical significance of the difference in ADH and GH responses during fentanyl and during alfentanil or sulfentanil anesthesia remains to be determined. However, this difference may provide part of the explanation why alfentanil and sufentanil-O2 anesthesia require less frequent employment of other anesthetic adjuvants and are easier to use than fentanyl during coronary artery surgery.

Prediction of outcome in acute renal failure

In an attempt to predict outcome in acute renal failure (ARF) we have utilized multiple logistic regression to analyze clinical data from 151 patients with ARF seen over a 15-month period. Recovery of renal function occurred in 60% of patients with a 58% survival. Our analysis demonstrated sepsis, respiratory failure, and oliguria to be the major predictors of nonrecovery of renal function. A logistic equation was generated for prediction of outcome and was validated in a second independent group of patients with ARF. Prediction of outcome could be achieved with a sensitivity of 75% and a specificity of 80%. Maximum sensitivity (100%) was associated with a 17% specificity, while maximum specificity (98%) yielded a sensitivity of 20%.

Plasma Antidiuretic Hormone Levels in Cardiac Surgical Patients during Morphine and Halothane Anesthesia

The effects of halothane and morphine anesthesia on plasma antidiuretic hormone (ADH) levels and urinary flow were determined in 18 patients undergoing elective open-heart operations. Patients were divided into three groups of six each: Group I, halothane, 0.5 per cent; Group II, morphine, 1 mg/ kg; Group til, morphine, 2 mg/kg. In addition, all patients received nitrous oxide - oxygen, 50 per cent each. Measurements of mean blood pressure; heart rate; urinary flow, osmolality and electrolytes; and plasma ADH (by radioimmunoassay) we remade prior to induction of anesthesia, 15 and 30 min after induction, and 15 and 30 min after surgical incision. Control values for ADH were comparable in all groups (about 3 pg/ml). There was no significant change in any group after induction of anesthesia. After surgical incision ADH levels increased significantly in Group I (102 ± 29 pg/ml), and Group II (42.6 ± 25 pg/ml), but not in Group III (14.5 ± 7 pg/ml). The increase of plasma ADH was significantly higher in Group I than in Group II or III. Variations in urinary (low were not significant throughout the study. These data demonstrate that neither morphine nor light halothane anesthesia stimulates high levels of ADH secretion. They suggest that the increase in ADH with surgical stimulation is a stress response that can be attenuated by deeper morphine anesthesia. The ADH levels arc beyond the physiologic range for antidiuretic action on the kidney, and may represent a vasopressor response. Variations in urinary flow were not ADH-related.

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.

RADIOIMMUNOASSAY OF ANTIDIURETIC HORMONE DURING MORPHINE ANAESTHESIA

SummaryThe effect of morphine anaesthesia on plasma antidiuretic hormone levels was studied in seven adult patients. Measurements of ADH showed no significant change with morphine and 50 per cent nitrous oxide. Significant elevation occurred with surgical stimulation as previously reported. Changes in urine flow with high doses of morphine are then not ADH related.RésuméUne étude des taux plasmatiques d’hormone antidiurétique a été effectuée par technique radio-immunologique, chez sept patients anesthésiés à la morphine ( 1 mg/kg ) et au protoxyde d’azote à 50 pour cent chirurgie à cœur ouvert.Quinze et trente minutes après administration de la morphine, les taux plasmatiques s’établissaient respectivement à 4.42 ± 2.6 µu/ml et à 4.14 ± 2.2 µu/mI, taux qui ne différaient pas de façon significative de ceux des contrôles faits avant administration de la morphine ( 3.21 ± 0.1 µu/ml).Ces taux se sont cependant élevés de façon significative 15 minutes après le début de la chirurgie (12.05 ± 0.4 µu/ml) et demeuraient élévés (8.29 ± 2.9 µu/ml) bien que plus bas après 30 minutes de chirurgie.Donc la morphine à doses anesthésiques combinée au protoxyde d’azote à 50 pour cent ne stimule pas la sécrétion d’HAD et les modifications du débit urinaire observées durant une anesthésie à la morphine ne sont pas liées à une stimulation de la sécrétion d’HAD par cet agent.

Effects of lithium on the kidney

ABSTRACT— We tested kidney function in 268 patients given lithium treatment for an average period of 37.6 months and in 59 manic‐depressive patients never given lithium. No patients suffered serious renal damage during the course of our observations. Maximum concentration capacity was lower and serum creatinine concentration higher in the lithium treated patients than in the controls, but the differences did not achieve statistical significance. Females had poorer concentrating ability than males, both among the control subjects and during lithium treatment. Concomitant antipsychotic drug therapy may affect concentrating ability and possibly glomerular function adversely.