Jörg Tarnow

Small, Oral Dose of Clonidine Reduces the Incidence of Intraoperative Myocardial Ischemia in Patients Having Vascular Surgery

Background Most new perioperative myocardial ischemic episodes occur in the absence of hypertension or tachycardia. The ability of alpha2 ‐adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients with coronary artery disease by increasing the myocardial oxygen supply‐and‐demand ratio. Methods A randomized double‐blind study design was used in 297 patients scheduled to have elective vascular surgical procedures to evaluate the effects of 2 micro gram/kg sup ‐1 oral clonidine (n = 145) or placebo (n = 152) on the incidence of perioperative myocardial ischemic episodes, myocardial infarction, and cardiac death. Continuous real‐time S‐T segment trend analysis (lead II and V5) was performed during anesthesia and surgery and correlated with arterial blood pressure and heart rate before and during ischemic events. Dose requirements for vasoactive and antiischemic drugs to control blood pressure and heart rate as well as episodes of myocardial ischemia (i.e., catecholamines, beta‐adrenoceptor antagonists, nitrates, and systemic vasodilators) and fluid volume load were recorded. Results Administration of clonidine reduced the incidence of perioperative myocardial ischemic episodes from 39% (59 of 152) to 24% (35 of 145) (P < 0.01). Hemodynamic patterns, percentage of ischemic time, and the number of ischemic episodes per patient did not differ. Nonfatal myocardial infarction developed after operation in four patients receiving placebo compared with none receiving clonidine (day 2 to 21; P = 0.07). The incidence of fatal cardiac events (1 vs. 2) was not different. Dose requirements for vasoactive and antiischemic drugs did not differ between the groups, but the amount of presurgical fluid volume was slightly greater in patients receiving clonidine (951 +/‐ 388 vs. 867 +/‐ 381 ml; P < 0.03). Conclusion A small oral dose of clonidine, given prophylactically, can reduce the incidence of perioperative myocardial ischemic episodes without affecting hemodynamic stability in patients with suspected or documented coronary artery disease.

Prostacyclin for the treatment of pulmonary hypertension in the adult respiratory distress syndrome: effects on pulmonary capillary pressure and ventilation-perfusion distributions.

Nine patients who had developed pulmonary artery hypertension during the adult respiratory distress syndrome (ARDS) were treated with an infusion of prostacyclin (PGI2) (12.5-35.0 ng.kg-1.min-1). Whether PGI2 might decrease the pulmonary capillary pressure (PCP) obtained by analysis of the pulmonary artery occlusion pressure decay curve and improve systemic oxygen delivery was examined. Gas exchange alterations induced by PGI2 were analyzed by using the multiple inert gas elimination technique. PGI2 reduced the pulmonary artery pressure from 35.6 to 28.8 mmHg (P less than 0.001) and the PCP from 22.9 to 19.7 mmHg (P less than 0.01) without changing the contribution of the pulmonary venous resistance to the total pulmonary vascular resistance. The cardiac index increased from 4.2 to 5.7 1.min-1.m-2 (P less than 0.001) due to both increased stroke volume and heart rate. Despite a marked deterioration of ventilation-perfusion (VA/Q) matching with increased true intrapulmonary shunt flow from 28.6% to 38.6% (P less than 0.01) of the cardiac output, the PaO2 was unchanged due to increased mixed venous oxygen content indicated by an augmented mixed venous PO2 (from 37.0 to 41.9 mmHg, P less than 0.01). This caused a 35% (P less than 0.001) increase of the systemic oxygen delivery rate. Thus, short-term infusions of PGI2 reduced PAP and PCP without deleterious effects on arterial oxygenation in patients with ARDS. Hence, PGI2 may be useful to lower pulmonary vascular pressures in patients with ARDS.

The effects of prostacyclin on gastric intramucosal pH in patients with septic shock

ObjectiveTo investigate whether infusing prostacyclin (PGI2) in patients with septic shock improves splanchnic oxygenation as assessed by gastric intramucosal pH (pHi).DesignInterventional clinical study.SettingSurgical ICU in a university hospital.Patients16 consecutive patients with septic shock according to the criteria of the ACCP/SCCM consensus conference all requiring norepinephrine to maintain arterial blood pressure.InterventionsAll patients received PGI2 (10 ng/kg·min) after no further increase in oxygen delivery could be obtained by volume expansion, red cell transfusion and dobutamine infusion. The results were compared with those before and after conventional resuscitation. The patients received continuous PGI2 infusion for 3–32 days.Measurements and resultsO2 uptake was measured directly in the respiratory gases, pHi was determined by tonometry. Baseline O2 delivery, O2 uptake and pHi were 466±122 ml/min·m2, 158±38 ml/min·m2, and 7.29±0.09, respectively. While O2 uptake remained unchanged, infusing PGI2 increased O2 delivery (from 610±140 to 682±155 ml/min·m2,p<0.01) and pHi (from 7.32±0.09 to 7.38±0.08,p<0.001) beyond the values obtained by conventional resuscitation. While 9 of 11 patients with final pHi>7.35 survived, all patients with final pHi<7.35 died (p<0.01).ConclusionsInfusing PGI2 in patients with septic shock increases pHi probably by enhancing blood flow to the splanchnic bed and thereby improves splanchnic oxygenation even when conventional resuscitation goals have been achieved.

Prostacyclin and right ventricular function in patients with pulmonary hypertension associated with ARDS

Eight patients who developed pulmonary artery hypertension during the adult respiratory distress syndrome (ARDS) were treated with an infusion of prostacyclin (PGI2, 12.5–35.0 ng·kg−1·min−1) for 45 min. We examined whether reducing the right ventricular (RV) outflow pressures by PGI2 infusion would increase the right ventricular ejection fraction (RVEF) measured by thermodilution. PGI2 reduced the pulmonary artery pressure (PAP) from 35.6 to 29.1 mmHg (p<0.01). The cardiac index (CI) increased from 4.2 to 5.81·min−1·m−2 (p<0.01) partly due to an increased stroke volume. The decreased PAP together with the increased CI resulted in a fall of the calculated pulmonary vascular resistance index (PVRI, from 5.1 to 2.5 mmHg·min·m2·1−1,p<0.01). In the patients with subnormal baseline RVEF the increased stroke volume was associated with an increased RVEF (from 47.6% to 51.8%,p<0.05) suggesting improved RV function. This result was underscored by a significant relationship between the changes in PVRI and RVEF (r=0.789, Δ% RVEF=−2.11·ΔPVRI-1.45). Despite an increased venous admixture from 27.8% to 36.9% (p<0.05) the arterial PO2 remained constant resulting in an increased oxygen delivery from 657 to 894 ml·min−1·m−2 (p<0.01). We conclude that short term infusions of PGI2 increased CI concomitant to improved RV function parameters when baseline RVEF was depressed. Since improved oxygen availability should be a major goal in the management of patients with ARDS PGI2 may be useful to lower pulmonary artery pressure in ARDS.

High Thoracic Epidural Anesthesia Does Not Alter Airway Resistance and Attenuates the Response to an Inhalational Provocation Test in Patients with Bronchial Hyperreactivity

BackgroundThe functional relevance of an intact pulmonary sympathetic innervatlon for airway resistance is unknown. We therefore evaluated whether or not pulmonary sympathetic denervation by thoracic epidural anesthesia decreases the threshold of an inhalational provocation with acetylcholine in 20 patients with documented bronchial hyperreactivity scheduled for elective upper abdominal or thoracic surgery. MethodsBaseline inhalational provocation with acetylcholine was performed 2–4 days before surgery. The acetylcholine threshold concentration for a hyperreactivity response (i.e., for a 20% decrease in forced expiratory volume in 1 s and a 100% increase in total respiratory resistance by oscillometry) was determined. On the day of surgery a second inhalatlve provocation with acetylcholine was performed 45 min after the patients had received 6–8 ml epidural bupivacaine 0.75% (n = 10), intravenous bupivacalne (1.2 mg * min-1, n = 6), or 6–8 ml epidural saline (n = 4). The acetylcholine threshold concentration for a hyperreactive response was again determined. We also measured vital capacity, forced expiratory volume in 1 s as a percentage of vital capacity, spread of sensory blockade (pin prick), skin temperature on hand and foot (telethermography). ResultsDuring thoracic epidural anesthesia, C4-T8 skin temperature increased significantly on hand and foot indicating widespread sympathetic blockade including the lungs. Compared to values obtained immediately before pulmonary sympathetic blockade, forced expiratory volume in 1 s as a percentage of vital capacity, and total respiratory resistance by oscillometry remained unchanged, while vital capacity decreased. Compared to baseline the acetylcholine threshold concentration for the hyperreactive response increased threefold after epidural as well as after intravenous bupivacaine. Epidural saline evoked no directional changes in the acetylcholine threshold concentration. ConclusionsWe conclude that in patients with bronchial hyperreactivity 1. blockade of pulmonary sympathetic innervation seems to be of no relevance for airway resistance and 2. both epidural and intravenous bupivacaine substantially attenuate the response to an inhalational provocation with acetylcholine.

Isoflurane Improves the Tolerance to Pacing-induced Myocardial Ischemia

Fourteen patients with normal, global, left ventricular function scheduled for elective myocardial revascularization were studied at rest and during atrial pacing before and during isoflurane anesthesia (0.5% end-tidal) plus 50% nitrous oxide. Rapid atrial pacing was performed in a stepwise fashion until the onset of angina pectoris in the awake patients. The same step increase in pacing rate was applied in the anesthetized patients. Compared with prepacing baseline values, isoflurane significantly decreased systemic blood pressure, coronary perfusion pressure, the rate-pressure product, and cardiac index. No patient had ST-segment depression while awake or during isoflurane anesthesia before pacing was started. Prepacing left and right ventricular filling pressures and wave forms were normal, both while awake and during isoflurane anesthesia. The mean pacing rate at which first signs of myocardial ischemia appeared (V5 ST-segment depression ≥0.1 mV, increase in pulmonary capillary wedge pressure (PCWP) to ≥15 mmHg, and prominent PCWP v-waves ≥20 mmHg) was significantly higher during isoflurane anesthesia than in the awake patients (128 ± vs. 115 ± 5 beats/min). With the exception of one patient, the individual pacing rates inducing first signs of ischemia in the awake patients were below the anginal threshold. None of the patients had a reduced ischemic threshold during anesthesia. Eleven anesthetized patients tolerated a higher pacing rate until initial signs of ischemia appeared. In four of these patients, the pacing rate required to induce first signs of ischemia was above the heart rate at which chest pain had been induced while they were awake. At a peak atrial pacing rate of 129 ‡ 5 beats/min, which had induced angina pectoris in the awake patients, the increase in PCWP was significantly smaller during pacing with isoflurane than during control pacing. Prominent PCWP v-waves (>20 mmHg) appeared in 12 of the 14 patients during initial pacing to angina and in eight patients paced during isoflurane anesthesia. In six of these eight patients, the abnormal v-waves were less prominent than those observed during control pacing. Ischemic ST-segment changes developed in 13 of 14 patients during initial pacing and in nine patients during pacing with isoflurane. Mean V5 ST-segment depression during the two pacing periods was significantly different, averaging 0.19 and 0.11 m V, respectively. The authors conclude that a low concentration of isoflurane plus nitrous oxide improves the tolerance to pacing-induced myocardial ischemia in patients with significant coronary artery disease.

Fat emulsions containing medium chain triglycerides in patients with sepsis syndrome : effects on pulmonary hemodynamics and gas exchange

Fat emulsions containing medium chain triglycerides (MCT) have recently been introduced into clinical practice as a component of total parenteral nutrition. Since several authors reported increased pulmonary artery pressure and impaired gas exchange during intravenous (i.v.) fat use, in particular in septic patients, we studied the pulmonary hemodynamic and gas exchange effects of i.v. fat containg MCT and long chain triglycerides (LCT) in patients with sepsis syndrome. As the effects of fat emulsions have been attributed to increased formation of prostanoids, the production of thromboxane A2 and prostacyclin was investigated by the determination of urinary thromboxane B2 and 6-keto-prostaglandin F2α, respectively. The i.v. fat use did not induce any alterations in pulmonary hemodynamics and gas exchange, the distribution of ventilation and perfusion nor urinary probably content. We conclude that fat emulsions containing MCT induce little alterations in pulmonary hemodynamics and gas exchange. This result is probably due to reduced prostaglandin formation because fat emulsions containing MCT provide less prostaglandin precursors than pure LCT emulsions.

Desflurane inhibits hypoxic pulmonary vasoconstriction in isolated rabbit lungs.

Background Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV) in vivo and in vitro with a half-maximum inhibiting effect (ED50) within concentrations applied for general anesthesia. Because it is unknown whether desflurane acts likewise, we studied its effect on HPV in isolated blood-perfused rabbit lungs and compared its ED sub 50 with that of halothane.

How Much Oxygen Does the Human Lung Consume

Background The amount of oxygen consumed by the lung itself is difficult to measure because it is included in whole‐body gas exchange. It may be increased markedly under pathological conditions such as lung infection or adult respiratory distress syndrome. To estimate normal oxygen consumption of the human lung as a basis for further studies, respiratory gas analysis during total cardiopulmonary bypass may be a simple approach because the pulmonary circulation is separated from systemic blood flow during this period. Methods Lung oxygen consumption was determined in 16 patients undergoing cardiac surgery. During total cardiopulmonary bypass their lungs were ventilated with low minute volumes (tidal volume, 150 ml; rate, 6 min sup ‐1; inspiratory oxygen fraction, 0.5; positive end‐expiratory pressure, 3 mmHg). All expiratory gas was collected and analyzed by indirect calorimetry. As a reference value also, whole‐body oxygen consumption of these patients was determined before total cardiopulmonary bypass. In a pilot study of eight additional patients (same ventilatory pattern), the contribution of systemic (bronchial) blood flow to pulmonary gas exchange during cardiopulmonary bypass was assessed. For this purpose, the amount of enflurane diffusing from the systemic blood into the bronchial system was measured. Results The human lung consumes about 5–6 ml oxygen per minute at an esophageal temperature of 28 degrees Celsius. Prebypass whole‐body oxygen consumption measured at nearly normothermic conditions was 198 +/‐ 28 ml/min. Mean lung and whole‐body respiratory quotients were similar (0.84 and 0.77, respectively). Extrapolating lung oxygen consumption to 36 degrees Celsius suggests that the lung consumes about 11 ml/min or about 5% of total body oxygen consumption. Because the amount of enflurane diffused from the systemic circulation into the bronchial system during cardiopulmonary bypass was less than 0.1%, the contribution of bronchial blood flow to lung gas exchange can be assumed to be negligible. Conclusion The lung consumes about 5% of whole‐body oxygen uptake.

Altered Hemodynamic Response to Dobutamine in Relation to the Degree of Preoperative β-Adrenoceplor Blockade

The relationship between the extent of preoperative β-adrenocepter blockade and the hemodynamic properties of dobutamine was investigated in patients scheduled for elective myocardial revascurization during isoflurane-nitrous oxide anesthesia. Twenty patients had been treated with β-adrenoceptor blocking drugs for at least 4 weeks before the study; 11 unblocked patients served as control group. The extent of clinical β-adrenoceptor blockade was quantified using the isoproterenol sensitivity test. The dose of isoroterenol required to increase heart rate by 25 beats/min was defined as the CD25 (chronotropic dose 25), representing the degree of β-adrenoceptor blockade. Geometric mean CD25/70 kg was 3.8 μg in the control group, and 24.5 μg in the patients receiving β-adrenoceptor blocking drugs. The authors found a significant inverse relationship between CD25 values and changes in cardiac index in response to three dobutamine infusion rates (1.0, 2.0, and 4.0 μg · kg−1 · min−1), the correlation coefficients being −0.78, −0.79, and −0.82, respectively. Compared to unblocked patients, almost no change, or even a decrease, of the cardiac index was observed at higher degrees of clinical β-adrenoceptor blockade. Moreover, there was a significant linear correlation (r = 0.66 - 0.75) between CD25 values and the effects of dobutamine on systemic vascular resistance index (SVRI), i.e., SVRI decreased in control patients, but increased in patients with high degrees of preoperative β-adrenoceptor blockade. This unmasked vasocontrictive response to dobutamine was observed despite the fact that the majority of our patients had received cardioselective adrenergic blocking drugs. No correlation existed between the extent of β-blockade and the effects of dobutamine on mean arterial blood pressure, and there was no difference in the effect of dobutamine on mean arterial blood pressure, whether the patient was beta blocked or not. The authors conclude that these results could have important clinical implications for the use of dobutamine in patients undergoing coronary artery bypass surgery who are receiving β-adrenoceptor blocking drugs for control of angina pectoris, hypertension, or arrhythmias.