Axel Goertz

Effect of vasopressin on hemodynamic variables, organ blood flow, and acid-base status in a pig model of cardiopulmonary resuscitation

Based upon the hypothesis that vasopressin (antidiuretic hormone) may increase vascular resistance during ventricular fibrillation, the effects of this potent vasoconstrictor were studied in a porcine model of ventricular fibrillation. Vasopressin therapy was compared to epinephrine by randomly allocating 14 pigs to receive either 0.045 mg/kg of epinephrine (n = 7) or 0.8 U/kg of vasopressin (n = 7) after 4 min of ventricular fibrillation and 3 min of open-chest cardiopulmonary resuscitation. During cardiopulmonary resuscitation, myocardial blood flow before and 90 s and 5 min after drug administration was 57 +/- 11, 84 +/- 11, and 59 +/- 9 mL.min-1 x 100 g-1 (mean +/- SEM) in the epinephrine group, and 61 +/- 5, 148 +/- 26, and 122 +/- 22 mL.min-1 x 100 g-1 in the vasopressin group (P < 0.05 at 90 s and 5 min). At the same times, mean cardiac index was not significantly different between the groups. After drug administration, coronary venous PCO2 was significantly higher and coronary venous pH was significantly lower in the epinephrine as compared to the vasopressin group. All pigs in both groups were resuscitated and survived the 2-h observation period. We conclude that vasopressin improves vital organ perfusion during ventricular fibrillation and cardiopulmonary resuscitation. Vasopressin seems to be at least as effective as epinephrine in this pig model of ventricular fibrillation.

Effect of 7.2% Hypertonic Saline/6% Hetastarch on Left Ventricular Contractility in Anesthetized Humans

Background Although a positive inotropic effect of hypertonic saline has been demonstrated in isolated cardiac tissue as well as in animal preparations, no information exists about a possible positive inotropic action of hypertonic saline in humans. The aim of this investigation was to determine whether a clinically relevant positive inotropic effect can be demonstrated in humans. Methods Twenty-six patients without cardiovascular disease were randomized to receive 4 ml/kg of either 7.2% hypertonic saline/6% hetastarch or 6% hetastarch (control) at a rate of 1 ml *symbol* kg sup -1 *symbol* min sup -1 while under general endotracheal anesthesia. Transesophageal echocardiography was used to evaluate left ventricular function. Arterial pressure, heart rate, and left ventricular end-systolic and end-diastolic diameter, area, and wall thickness were measured immediately before and after administration of either solution. Fractional area change, end-systolic wall stress, and the area under the end-systolic pressure-length relationship curve (ESPLRarea) were calculated. ESPLRarea was used to assess left ventricular contractility. Results Administration of hypertonic saline/hetastarch resulted in a significant decrease of mean arterial pressure and end-systolic wall stress from 77 plus/minus 14 (mean plus/minus SD) to 64 plus/minus 17 mmHg (P < 0.01) and from 52 plus/minus 14 to 32 plus/minus 11 103 dyne/cm2 (P > 0.01), respectively. End-diastolic area and fractional area change increased from 16.5 plus/minus 2.9 to 21.7 plus/minus 3.3 cm2 (P < 0.01) and from 0.53 plus/minus 0.07 to 0.70 plus/minus 0.06 (P < 0.01), respectively, whereas there was only a minor change of ESPLRarea from 38 plus/minus 13 to 44 plus/minus 13 mmHg.cm (P < 0.05). Conclusions The apparent improvement of left ventricular systolic function in response to hypertonic saline/hetastarch is caused mainly by the combined effect of increased left ventricular preload and reduced left ventricular afterload. A possible positive inotropic action of hypertonic saline/hetastarch is not likely to be clinically relevant.

Understanding the mechanisms by which isoflurane modifies the hyperglycemic response to surgery.

We studied the effect of anesthesia on the kinetics of perioperative glucose metabolism by using stable isotope tracers. Twenty-three patients undergoing cystoprostatectomy were randomly assigned to receive epidural analgesia combined with general anesthesia (n = 8), fentanyl and midazolam anesthesia (n = 8), or inhaled anesthesia with isoflurane (n = 7). Whole-body glucose production and glucose clearance were measured before and during surgery. Glucose clearance significantly decreased during surgery independent of the type of anesthesia. Epidural analgesia caused a significant decrease in glucose production from 10.2 ± 0.4 to 9.0 ± 0.4 &mgr;mol · kg−1 · min−1 (P < 0.05), whereas the plasma glucose concentration was not altered (before surgery, 5.0 ± 0.2 mmol/L; during surgery, 5.2 ± 0.1 mmol/L). Glucose production did not significantly change during fentanyl/midazolam anesthesia (before surgery, 10.5 ± 0.5 &mgr;mol · kg−1 · min−1; during surgery, 10.1 ± 0.5 &mgr;mol · kg−1 · min−1), but plasma glucose concentration significantly increased from 4.8 ± 0.1 mmol/L to 5.3 ± 0.2 mmol/L during surgery (P < 0.05). Isoflurane anesthesia caused a significant increase in plasma glucose concentration (from 5.2 ± 0.1 mmol/L to 7.2 ± 0.5 mmol/L) and glucose production (from 10.8 ± 0.5 &mgr;mol · kg−1 · min−1 to 12.4 ± 1.0 &mgr;mol · kg−1 · min−1) (P < 0.05). Epidural analgesia prevented the hyperglycemic response to surgery by a decrease in glucose production. The increased glucose plasma concentration during fentanyl/midazolam anesthesia was caused by a decrease in whole-body glucose clearance. The hyperglycemic response observed during isoflurane anesthesia was a consequence of both impaired glucose clearance and increased glucose production.

Hemodynamic and metabolic effects of epinephrine during cardiopulmonary resuscitation in a pig model.

Background and MethodsThis study was designed to assess the effect of epinephrine during cardiopulmonary resuscitation (CPR) on left ventricular myocardial blood flow, systemic oxygen delivery and consumption, and on plasma glucose and lactate concentrations. Fourteen pigs were allocated to receive either 0.9% saline (n = 7), or 45 μg/kg epinephrine (n = 7) after 5 mins of ventricular fibrillation, and 3 mins of open-chest CPR. Left ventricular myocardial blood flow was measured with radiolabeled microspheres. Plasma catecholamine concentrations were measured by high-pressure liquid chromatography. ResultsDuring open-chest CPR, mean (± SD) values of left ventricular myocardial blood flow before, 90 sees, and 5 mins following drug administration were 49 ± 10, 46 ± 12, 43 ± 15 mL/min/100 g, respectively, in the control group, and 52 ± 12, 118 ± 21, 84 ± 28 mL/min/100 g, respectively, in the epinephrine group (p < .05 at 90 sees and 5 mins). At the same time points, mean (± SD) oxygen delivery indices were 7.7 ± 3.0, 6.0 ± 2.1, 6.5 ± 2.7 mL/min/kg in the control group and 7.6 ± 2.5, 5.3 ± 2.1, 5.5 ± 1.9 mL/min/kg in the epinephrine group (nonsignificant). Mean oxygen consumption indices were 5.8 ± 2.4,4.6 ± 1.6, 5.2 ± 2.6 mL/min/kg in the control group and 5.4 ± 1.6, 4.2 ± 1.6, 4.4 ± 1.4 mL/min/kg in the epinephrine group (nonsignificant). During CPR and before epinephrine administration, arterial plasma epinephrine concentrations increased from prearrest values of 0.77 ± 0.70 to 62.1 ± 48.7 μg/L, and plasma norepinephrine concentrations increased from 0.28 ± 0.32 to 104.3 ± 57.1 μg/L. After administered epinephrine, there was an additional increase to 271 ± 83 μg/L at 90 sees in arterial plasma epinephrine, but no important alteration in the plasma norepinephrine concentration. At no time point could we find a clinically important difference in plasma glucose or lactate concentrations between the two groups. ConclusionsAt a dose of 45 μg/kg, epinephrine caused an increase in left ventricular myocardial blood flow after a total of 8 mins of cardiac arrest, including 3 mins of CPR, while not altering systemic oxygen delivery and consumption, plasma glucose, or lactate concentrations.

Effect of phenylephrine bolus administration on global left ventricular function in patients with coronary artery disease and patients with valvular aortic stenosis.

Background:Although phenylephrine bolus administration is frequently used to increase coronary perfusion pressure in patients with coronary artery disease or valvular aortic stenosis, there are no data describing its effect on left ventricular function (LVF) Methods:Twenty patients scheduled for elective coronary artery bypass grafting (group 1) and 18 patients scheduled for elective aortic valve replacement (group 2) entered the study. The effect of phenylephrine was compared with that of norepinephrine in those patients who developed a defined degree of arterial hypotension under general anesthesia. These patients were randomized to receive an initial bolus of either phenylephrine (1 μg/kg) or norepinephrine (0.05 μg/kg) followed by a bolus of the other drug after arterial pressure and heart rate (HR) had returned to baseline. Transesophageal echocardiography was used to evaluate LVF. Arterial pressure, HR, ejection time, and LV diameter, area, and wall thickness were recorded immediately before and for 3 min after bolus administration. Fractional diameter shortening, fractional area change, mean heart rate corrected velocity of circumferential fiber shortening (mVcfc), and LV meridional endsystolic wall stress (ESWS) were calculated. Results:Both substances effectively restored arterial pressure in both groups. However, in group 1, phenylephrine administration resulted in a reduction of fractional area change from 0.51 (median) to 0.39 (P=0.0007) and a reduction of mVcfcfrom 1.16 to 0.61 circ/s (P=0.0001). End-systolic wall stress increased from 98 to 186 103 dyne · cm-2 (P=0.0001). Administration of norepinephrine to group 1 and administration of either substance to the group 2 patients did not cause any significant changes of LVF Conclusions:The results indicate that phenylephrine given as an intravenous bolus to patients with CAD anesthetized with fentanyl causes a transient impairment of LV global function and that phenylephrine bolus administration is well tolerated in patients with valvular aortic stenosis

Influence of high thoracic epidural anesthesia on left ventricular contractility assessed using the end-systolic pressure-length relationship

The effect of high thoracic epidural anesthesia (TEA) on left ventricular contractility was studied in a prospective clinical trial. Forty‐eight patients with ASA physical status 1 and 2 and without cardiovascular disease were included in the study. Thirty‐six patients scheduled for elective upper abdominal surgery were randomly assigned to Group 1 (TEA, bupivacaine 0.25%, n= 12), Group 2 (TEA, bupivacaine 0.5%, n = 12) or to Group 3 (control without TEA, n= 12). TEA induced a sensory block which extended over all cardiac segments. In order to assess the effect of systemically absorbed bupivacaine, we studied a separate group of patients who received lumbar epidural anesthesia without involvement of the cardiac segments: Group 4 (LEA, bupivacaine 0.5%, n= 10). Left ventricular contractility was assessed using the end‐systolic pressure‐length relationship. Left ventricular dimensions were measured by transesophageal echocardiography. All hemodynamic measurements were performed under general anesthesia. There was no significant difference in systolic or diastolic arterial pressure, heart rate, left ventricular end‐systolic and end‐diastolic cross‐sectional areas and left ventricular wall stress between the four groups. Left ventricular maximum elastance as a measure of left ventricular contractility was significantly (P<0.001) reduced in Groups 1 and 2 [8.1 (±3.5) and 9.6 (±4.4) kPa · cm‐1, respectively] as compared to Groups 3 and 4 [18.4 (±8.8) and 17.7 (±7.7) kPa · cm‐1, respectively]. No significant difference could be demonstrated between Groups 1 and 2 or between Groups 3 and 4. It is concluded that high TEA severely alters left ventricular contractility even in subjects without pre‐existing cardiac disease.

Analgesic and hemodynamic effects of epidural clonidine, clonidine/morphine, and morphine after pancreatic surgery--a double-blind study.

This study characterizes analgesia and hemodynamics after epidural clonidine 8 micro gram/kg (Group C) or clonidine 4 micro gram/kg + morphine 2 mg (Group CM) in comparison to epidural morphine 50 micro gram/kg (Group M).Forty-five patients scheduled for pancreatectomy in combined general/epidural anesthesia were studied. The study drugs were administered 75 min postoperatively and for 10 h pain intensity (visual analog scale [VAS]), heart rate (HR), mean arterial pressure (MAP), and cardiac output (CO) were measured; filling pressures were kept >5 mm Hg. Adequate analgesia could be achieved within 1 h in all patients of Groups C and CM, but only in six patients of Group M (P < 0.001). Quality of analgesia was comparable in all groups (VAS reduction 82% +/- 20%, mean +/- SD) but duration of analgesic action was longer in Groups CM (586 +/- 217 min) and M (775 +/- 378 min) compared to Group C (336 +/- 119 min) (P < 0.001). In Group M, no hemodynamic alterations occurred. In Groups C and CM, HR, CO, and MAP were reduced significantly compared to baseline within the first 15-90 min, while stroke volume and systemic vascular resistance remained stable. We conclude, that hemodynamic alteration after epidural clonidine under conditions of stable filling pressures is caused mainly by a decrease in HR. It is not an effect of analgesia but of the intrinsic antihypertensive action of clonidine. (Anesth Analg 1995;80:869-74)

Influence of Phenylephrine Bolus Administration on Left Ventricular Filling Dynamics in Patients with Coronary Artery Disease and Patients with Valvular Aortic Stenosis

BackgroundLeft ventricular diastolic function Is known to be impaired in patients with coronary artery disease and patients with valvular aortic stenosis. Phenylephrine is frequently administered as an Intravenous bolus in these patients perioperatively to increase coronary perfusion pressure. Although this is common practice, there is no information about the effect of phenylephrine bolus administration on left ventricular filling dynamics. MethodsTwenty patients with coronary artery disease (group 1), 15 patients with valvular aortic stenosis (group 2), and 10 subjects without cardiovascular disease (group 3, control) entered the study. Left ventricular filling was evaluated using transesophageal pulsed Doppler echocardiography before and after phenylephrine Injection given to patients whose mean blood pressure has decreased by more than 20% (and was not higher than 90 mmHg). We recorded the transmitral blood flow velocity curve and measured peak early and peak atrial flow velocity, acceleration and deceleration time of the early flow velocity peak, and mitral valve diameter. We calculated the ratio of peak early to peak atrial flow velocity (PE/PA), acceleration and deceleration rate of the early flow peak, and peak filling rate. ResultsPhenylephrine effectively restored arterial pressure in all three groups. However, in group 1, phenylephrine administration resulted in a reduction of PE/PA, acceleration rate of the early flow peak, and peak filling rate from 1.25 (mean) to 0.75 (P < 0.001), 411 to 276 cm/s2 (P < 0.001), and 439 to 305 ml/s (P < 0.001), respectively. In contrast, in group 2, intravenous phenylephrine Increased PE/PA, acceleration rate of the early flow peak, and peak filling rate from 0.76 to 0.97 (P < 0.001), 365 to 503 cm/s2 (P < 0.05), and 321 to 388 ml/s (P < 0.01), respectively. In the control subjects, phenylephrine caused a transient reduction of PE/PA and peak filling rate from 1.71 to 1.39 (P <0.001) and 618 to 524 ml·s-1(P < 0.001), respectively. ConclusionsPhenylephrine bolus administration causes an alteration of left ventricular filling In coronary artery disease patients that seems to be more marked than that seen In normal subjects. In patients with aortic stenosis no deleterious effects were observed in response to phenylephrine.

The effect of ephedrine bolus administration on left ventricular loading and systolic performance during high thoracic epidural anesthesia combined with general anesthesia.

We investigated the effect of ephedrine on left ventricular function in patients without cardiovascular disease under high thoracic epidural anesthesia combined with general anesthesia. Because the epidural block was extended to all cardiac segments, ephedrine was assumed to be deprived of its centrally mediated actions. Left ventricular (LV) function was assessed using transesophageal echocardiography. We measured arterial pressure (AP), heart rate (HR), LV end-systolic and end-diastolic diameter and area (ESA, EDA), wall thickness, and LV ejection time before and after intravenous ephedrine bolus administration. We calculated area ejection fraction (EFA), end-systolic wall stress (ESWS), and mean velocity of circumferential fiber shortening (mVcfc). Ephedrine had a biphasic effect on left ventricular function. It transiently decreased EDA from 18.9 to 16.5 cm2 (mean), whereas EFA and mVcfc were increased from 33% to 49%, and from 1.88 to 2.67 circumferences/s, respectively. During the second phase, ephedrine increased mean arterial pressure (MAP) from a baseline value of 62 to 87 mm Hg, EDA was restored to 19.3 cm2, and EFA and mVcfc remained above baseline (52% and 2.64 circumferences/s, respectively). ESWS was not significantly increased from baseline. We conclude that ephedrine improves left ventricular contractility, even in the presence of high thoracic epidural anesthesia, without causing relevant changes of left ventricular afterload.

Influence of Vaginal Versus Abdominal Hysterectomy on Perioperative Glucose Metabolism

The aim of this study was to investigate the metabolic effects of abdominal versus vaginal hysterectomy with specific regard to perioperative glucose metabolism.Fourteen patients received either abdominal (AH, n = 7) or vaginal hysterectomy (VH, n = 7). Hepatic glucose production was measured before and 2.5 h after the operation by stable isotope technique ([6,6-(2) H2]-glucose). Metabolic substrates (glucose, lactate, nonesterified fatty acids [NEFA], beta-hydroxybutyrate) and hormones (insulin, glucagon, cortisol, catecholamines) were determined pre-, intra-, and postoperatively. VH induced a higher postoperative glucose concentration than the abdominal approach (VH, 148 +/- 25 mg/dL; AH, 111 +/- 16 mg/dL; P < 0.05). Since postoperative enhancement of hepatic glucose production was comparable in both groups, glucose clearance was lower after the vaginal procedure (VH, 1.7 +/- 0.3 mL [centered dot] kg-1 [centered dot] min-1; AH, 2.1 +/- 0.3 mL [centered dot] kg-1 [centered dot] min-1; P < 0.05). NEFA, beta-hydroxybutyrate, and catecholamines similarily increased after surgery. Cortisol levels were more increased after VH (VH, 80 +/- 26 micro g/dL; AH, 37 +/- 14 micro g/dL; P < 0.001). Lactate, glucagon, and insulin concentrations did not change perioperatively. The more pronounced hyperglycemic response to VH was due to lower peripheral glucose use caused by higher postoperative cortisol values. The mechanisms responsible for this marked cortisol enhancement after the vaginal operation as well as the clinical significance for patients with preexisting impaired carbohydrate tolerance, however, remained unclear and warrant further investigation. (Anesth Analg 1996;83:991-5)