Direct comparison of the effects of nebulized nitroprusside versus inhaled nitric oxide on pulmonary and systemic hemodynamics during hypoxia-induced pulmonary hypertension in piglets

OBJECTIVE: To test the hypothesis that nebulized nitroprusside and inhaled nitric oxide would not differ in producing selective pulmonary vasodilation during hypoxia-induced pulmonary hypertension in piglets. SETTING: University laboratory. SUBJECTS: Five piglets. INTERVENTIONS: Piglets (n = 5) were anesthetized and instrumented to monitor systemic arterial pressure, pulmonary artery pressure, and cardiac output continuously. Hypoxia was induced (DeltaFio2 from 0.5 to 0.08), and either nebulized nitroprusside (5 mg/mL at 4 L/min flow; total dose 25 mg) or inhaled nitric oxide (20 ppm) was introduced into the ventilator circuit for 15 mins. Normoxia was then restored, and a repeat cycle of hypoxia followed by the alternate vasodilator treatment was initiated. MEASUREMENTS AND MAIN RESULTS: Hypoxia significantly reduced Pao2 (from 206 to 30 torr) and elevated pulmonary artery pressure (from 18 to 33 torr) while not significantly affecting systemic arterial pressure or cardiac output. During hypoxia, inhaled nitric oxide reduced pulmonary artery pressure from 33 to 21 torr (p <.01), whereas systemic arterial pressure and cardiac output were unchanged. During hypoxia, nebulized nitroprusside also reduced pulmonary artery pressure from 33 to 23 mm Hg (p <.01; p = nonsignificant vs. inhaled nitric oxide), whereas systemic arterial pressure and cardiac output again remained constant. The time course of the reduction in pulmonary artery pressure during inhaled nitric oxide was roughly ten-fold more rapid (<5 secs) than during nebulized nitroprusside ( approximately 1 min). Neither inhaled nitric oxide nor nebulized nitroprusside altered pH, Pao2, or Paco2. CONCLUSION: Both inhaled nitric oxide and nebulized nitroprusside produced prompt, significant, selective reduction of pulmonary artery pressure and pulmonary vascular resistance in piglets with hypoxia-induced pulmonary hypertension, without apparent effects on systemic hemodynamics or pulmonary gas exchange. The equivalence of the two effects in this animal model suggests that cautious extrapolation of the use of nebulized nitroprusside as a convenient bridge to inhaled nitric oxide in selected clinical contexts for human infants may be warranted.     

Effect of acute moderate changes in PaCO2 on global hemodynamics and gastric perfusion

OBJECTIVE: To describe global hemodynamics and splanchnic perfusion changes in response to acute modifications in Paco2 in hemodynamically stable patients. DESIGN: Prospective, randomized crossover study. SETTING: Medical-surgical intensive care unit at a community hospital (400,000 inhabitants). PATIENTS: Ten critically ill patients who were sedated, paralyzed, and mechanically ventilated. INTERVENTIONS: Hypercapnia and hypocapnia were obtained by increasing and reducing instrumental deadspace in random order. After each intervention, patients returned to the basal condition. Each period lasted 80 min: 20 min to achieve stable Paco2 and 60 min for tonometer equilibration. In each period, global hemodynamic variables and tonometric data were collected. The periods were compared using analysis of variance. MEASUREMENTS AND MAIN RESULTS: Acute hypercapnia (Paco2 from 40+/-3 to 52+/-3 torr, p<.05) increased cardiac index (3.43+/-0.37 vs. 3.97+/-0.43 mL/min/m2, p<.05), heart rate (95+/-6 vs. 105+/-3 beats/min, p<.05), and mean pulmonary artery pressure (21+/-1 vs. 24+/-1 mm Hg, p<.05) and reduced systemic vascular resistance (992+/-98 vs. 813+/-93 dyne x sec/ cm5, p<.05) and oxygen extraction ratio (27+/-3% vs. 22+/-2%, p<.05). Standardized intramucosal Pco2 increased from 49+/-2 to 61+/-3 torr (p<.05) with an associated decrease in calculated intramucosal pH ([pHi] 7.35+/-0.03 vs. 7.25+/-0.02, p<.05), but the gastro-arterial Pco2 gradient (deltaPco2) did not change. Acute hypocapnia (Paco2 from 41+/-3 to 34+/-3 torr, p<.05; pH 7.41+/-0.01 to 7.47+/-0.02, p<.05) induced slight increments in systemic vascular resistance (995+/-117 vs. 1088 +/- 160 dyne x sec/cm5, p<.05) and oxygen extraction ratio (28+/-2% vs. 30+/-2%, p<.05). Standardized intramucosal Pco2 decreased (50+/-4 vs. 44+/-3 torr, p<.05), pHi increased (7.33+/-0.03 vs. 7.36+/-0.02; p<.05), but deltaPco2 did not change. CONCLUSIONS: In this small group of stable patients, moderate acute variations in Paco2 had a significant effect on global hemodynamics, but splanchnic perfusion, assessed by deltaPco2, did not change. In these conditions, the use of pHi to evaluate gastric perfusion appears unreliable.     

Naloxone improves arterial blood pressure and hypoxic ventilatory depression, but not survival, of rats during acute hypoxia

OBJECTIVE: To investigate the effects of naloxone and morphine during acute hypoxia. DESIGN: Prospective, randomized animal study. SETTING: University laboratory. SUBJECTS: Twenty-eight adult male Sprague Dawley rats, weighing 300-350 g. INTERVENTIONS: The rats were implanted with a femoral catheter and subcutaneous electrodes for electrocardiogram recording and were randomly assigned to receive morphine (5 mg/kg), naloxone (5 mg and 10 mg/kg), or normal saline (control) (n = 7 in each). Fifteen minutes after intraperitoneal injection of the drug, each rat was exposed to hypoxic gas (5% oxygen, 95% N2) for 70 mins. Hypoxic survival time was measured. Mean arterial pressure (MAP), arterial pH, Paco2, Pao2, and base excess were measured before injection (baseline), 14 mins after injection (H0), and 6 mins (H1), 33 mins (H2), and 48 mins (H3) after exposure to hypoxia. MEASUREMENTS AND MAIN RESULTS: Hypoxic survival was similar between the naloxone 5 mg/kg and control groups (p = .183), significantly lower in the naloxone 10 mg/kg group (p < .01), and significantly higher in the morphine 5 mg/kg group (p < .05) compared with controls. MAP significantly decreased in all groups. However, at H2-H3, MAP was better preserved in both naloxone groups and was lower in the morphine group compared with controls. Paco2 was maintained higher at H0-H3 in the morphine group and lower at H2-H3 in both naloxone groups compared with controls. CONCLUSION: During acute hypoxia, naloxone preserves arterial blood pressure and attenuates hypoxic ventilatory depression by antagonizing endogenous opiates, but it does not improve hypoxic survival. In contrast, morphine, which enhances the action of endogenous opiates, does improve hypoxic survival. The acute hypoxic tolerance of morphine may be partly attributable to a depression of oxygen consumption, increased cerebral blood flow secondary to high Paco2, and protective actions mediated by delta-opioid receptors.     

Carbon dioxide homeostasis during laparoscopy.

Arterial blood gases were monitored in ten patients undergoing laparoscopy for diagnostic or sterilization procedure. During constant volume of ventilation, mean arterial co2 tension rose approximately 5 torr following insufflation of the peritoneal cavity with carbon dioxide. Arterial pH changes correlated well with arterial Pco2 changes. There was no significant change of oxygen tension in these patients.     

Transcutaneous PCO2 monitoring in critically ill adults: clinical evaluation of a new sensor

OBJECTIVE: In critically ill patients, arterial blood gas analysis is the gold standard for evaluating systemic oxygenation and carbon dioxide partial pressure. A new miniaturized carbon dioxide tension Pco2-Spo2 single sensor (TOSCA, Linde Medical Sensors AG, Basel, Switzerland) continuously and noninvasively (transcutaneously) monitors both Paco2 and oxygen saturation by pulse oximetry (Spo2). The present study was designed to investigate the usability and the accuracy of this device in critically ill patients. DESIGN: Prospective clinical investigation. SETTING: A 20-bed, university-affiliated, surgical intensive care unit. PATIENTS: Patients admitted after major surgery, multiple trauma, or septic shock equipped with an arterial catheter. INTERVENTIONS: The heated (42 degrees C) sensor was fixed at the earlobe using an attachment clip. Transcutaneous Pco2 (TcPco2) measurements were correlated with Paco2 values (measured using a blood gas analyzer). In addition, the differences between Paco2 and TcPco2 values were evaluated using the method of Bland-Altman. MEASUREMENTS AND MAIN RESULTS: We studied 55 patients, aged 18-80 (mean 57 +/- 15) yrs. A total of 417 paired measurements were compared. Correlation between TcPco2 and Paco2 was r = .86 (p < .01) in the Paco2 range of 24-101 mm Hg. Mean bias (+/-sd) between the two methods of measurement (Bland-Altman analysis) was 1.2 +/- 6.0 mm Hg with TcPco2 slightly overestimating arterial carbon dioxide tension. Nineteen percent of the measured values were outside of the acceptable clinical range of agreement of +/-7.5 mm Hg. CONCLUSIONS: The present study suggests that Paco2 can be acceptably assessed by measuring TcPco2 using the TOSCA Pco2-Spo2 sensor.     

Neonatal cerebral oxygen regulation after hypothermic cardiopulmonary bypass and circulatory arrest

OBJECTIVE: Despite technical advances, neurologic sequelae continue to occur in neonates after heart surgery using deep hypothermic cardiopulmonary bypass (dhCPB) and circulatory arrest (DHCA). This study sought to determine the cerebral microcirculatory responses to hypoxia, hypotension, hypocapnia, and hypercapnia after dhCPB and DHCA. DESIGN: Prospective laboratory animal trial. SETTING: Research laboratory. SUBJECTS: Twenty-eight newborn pigs. INTERVENTIONS: Piglets were divided into control, dhCPB, and DHCA groups. The control group received surgery. The dhCPB group received surgery and deep hypothermic CPB for 40 mins. The DHCA group received surgery, deep hypothermic CPB for 40 mins, and circulatory arrest for 60 mins. Two hours after the intervention, cerebral microcirculatory responses were examined. MEASUREMENTS AND MAIN RESULTS: Cerebral microcirculatory responses consisted of changes in cerebral oxygen saturation (Sco2) and pial arteriolar diameter measured by near- infrared spectroscopy and intravital microscopy, respectively. All groups experienced similar decreases in Sco2 and increases in pial arteriolar diameter in response to moderate and severe hypoxia (Pao2, 35 and 25 torr, respectively) and moderate and severe hypotension (mean pressure, 30 and 20 mm Hg, respectively). Sco2 and pial arteriolar diameter decreased to hypocapnia (Paco2, 25 torr) similarly in all groups. To hypercapnia (Paco2, 70 torr), Sco2 increased in the control group, did not change in the dhCPB group, and decreased in the DHCA group. Pial arteriolar diameter to hypercapnia increased in the control and the dhCPB groups but did not change in the DHCA group. CONCLUSIONS: Cerebral vascular and oxygenation responses to hypoxia, hypocapnia, and hypotension were preserved after dhCPB and 1 hr of DHCA. By comparison, cerebral vascular and oxygenation responses to hypercapnia were not; both vascular and oxygenation responses were altered after DHCA, but only the oxygenation response was altered after dhCPB. These data suggest a selective disturbance in the microcirculation and/or parenchymal oxygen metabolism after DHCA and dhCPB.     

Gut mucosal-arterial Pco2 gradient as an indicator of splanchnic perfusion during systemic hypo- and hypercapnia

OBJECTIVES: By accounting for influences of systemic acid-base disturbances, gut mucosal-arterial Pco2 gradient (Pico2 - Paco2) has been increasingly advocated as a more specific marker of splanchnic perfusion than Pico2 alone. We examined the stability of the Pico2 - Paco2 gradient compared with raw Pico2 measurements during induced systemic hypo- and hypercapnia. DESIGN: A prospective animal study. SETTINGS: A university research laboratory. SUBJECTS: Twenty anesthetized, paralyzed, and mechanically ventilated mongrel dogs. INTERVENTIONS: After a baseline period during which Paco2 was maintained near 40 torr, the animals were divided into four groups. Minute ventilation was then altered by adjusting tidal volume, frequency, or both to achieve group Paco2 values of 15, 20, 60, and 80 torr for groups 1 through 4, respectively. Portal blood flow was monitored and maintained near baseline levels by infusion of intravenous fluids. Intestinal Pico2 was measured continuously by using capnometric recirculating gas tonometry. MEASUREMENTS AND MAIN RESULTS: Mean (+/- SE) aggregate baseline Pico2 - Paco2 was 16.9+/-3.3 torr. After 60 mins of hypoventilation, Pico2 - Paco2 decreased to 14.2+/-1.1 and to 13.7+/-2.7 torr in groups 3 and 4, respectively (p = NS, compared with baseline for both). On the other hand, after 60 mins of hyperventilation, Pico2 - Paco2 increased to 37.9+/-3.6 and 28.0+/-6.3 torr in groups 1 and 2, respectively (p < .0001, compared with baseline for both). CONCLUSIONS: In this model of maintained portal blood flow, Pico2 - Paco2 remained essentially stable after hypoventilation but increased significantly after inducing hyperventilation. Our findings warrant cautious interpretation of Pico2 - Paco2 as an indicator of splanchnic perfusion during systemic hypocapnia.     

Effect of carbon dioxide on systemic oxygenation, oxygen consumption, and blood lactate levels after bidirectional superior cavopulmonary anastomosis

OBJECTIVE: We sought to assess the effects of four different CO2 tensions on systemic oxygenation, oxygen consumption, and arterial blood lactate levels early after bidirectional superior cavopulmonary anastomosis. DESIGN: Prospective study. SETTING: Quaternary pediatric cardiac critical care unit. PATIENTS: Nine children aged 2-23 months (median, 7 months). INTERVENTIONS: All patients were sedated, muscle relaxed, and mechanically ventilated. Baseline Paco2 was adjusted to 35 mm Hg by changing tidal volume. CO2 was added via the inlet port of the ventilator to maintain the Paco2 at 45 and 55 mm Hg. Measurements were repeated after discontinuing additional CO2 gas at a Paco2 of 40 mm Hg. Arterial blood gases and lactate were measured at each level of Paco2. We measured oxygen consumption continuously by respiratory mass spectrometry. MEASUREMENTS AND MAIN RESULTS: Mean (95% confidence interval) Paco2 increased from 35 (34-36) to 45 (44-46) to 55 (54-56) mm Hg (4.7 [4.5-4.9] to 6 [5.7-6.3] to 7.3 [7.2-7.4] kPa), arterial pH decreased from 7.43 (7.39-7.47) to 7.35 (7.31-7.39) to 7.28 (7.24-7.32). Pao2 increased from 36 (32-40) to 44 (40-48) to 50 (45-55) mm Hg (4.8 [4.3-5.3] to 5.9 [5.4-6.4] to 6.7 [6.2-7.2] kPa), and oxygen saturation increased from 72% (67-79%) to 77% (73-81%) to 80% (76-84%). Oxygen consumption decreased significantly, with each increase in Paco2, from 146 (125-167) to 132 (112-152) to 126 (107-145) mL.min.m (p = .0001), and lactate decreased from 1.5 (1-2.0) to 1.2 (0.8-1.6) to 0.8 (0.5-1.1) mmol/L (p < .01). These changes returned toward baseline at a Paco2 of 40 mm Hg. CONCLUSIONS: Moderate hypercapnia with respiratory acidosis improved arterial oxygenation and reduced oxygen consumption and arterial lactate levels, thus improving overall oxygen transport in children after bidirectional superior cavopulmonary anastomosis.     

Resuscitation from experimental heatstroke by hyperbaric oxygen therapy

OBJECTIVE: Heatstroke is characterized by hyperthermia, vasoplegic shock, and cerebral ischemia and hypoxia. Hyperbaric oxygen (HBO) has been shown to reduce brain ischemia and behavioral dysfunction during cerebral artery occlusion. The efficacy of HBO therapy for resuscitation from heatstroke remains to be determined in the laboratory. DESIGN: Anesthetized rats were randomized to several groups and administered: 1) no resuscitation (normobaric air) after onset of heatstroke, 2) HBO for 1 hr (100% oxygen at 253 kPa for 1 hr), 3) cyclic HBO intermitted by a 5-min air break for 1 hr of treatment (100% oxygen at 253 kPa), 4) hyperbaric air (air at 253 kPa for 1 hr), 5) normobaric hyperoxia (100% oxygen at 101 kPa for 1 hr), or 6) 8% HBO (hyperbaric 8% oxygen at 253 kPa for 1 hr). SETTING: Laboratory investigation. SUBJECTS: Sprague-Dawley rats (300- to 400-g males). INTERVENTIONS: Rats were exposed to an ambient temperature of 43 degrees C to induce heatstroke. Their colonic temperature; mean arterial pressure; heart rate; arterial blood levels of pH, Paco2, Pao2, So2%, and tumor necrosis factor-alpha; the cortical levels of ischemic and damage markers, and cortical neuronal damage scores were determined. The moment at which mean arterial pressure began to decrease from peak levels was arbitrarily taken as the onset of heatstroke. MAIN RESULTS: Survival time (interval between onset of heatstroke and animal death) was 19 +/- 1 (n = 10), 131 +/- 18 (n = 14), 159 +/- 28 (n = 13), 72 +/- 14 (n = 10), 68 +/- 12 (n = 10), and 45 +/- 11 (n = 10) mins, respectively, for normobaric air, HBO for 1 hr, cyclic HBO, hyperbaric air, normobaric hyperoxia, and 8% HBO groups. The heatstroke induced arterial hypotension and bradycardia, decreased arterial levels of pH, Pao2, and So2%, increased arterial levels of tumor necrosis factor-alpha, and increased values of cellular ischemia and damage markers. In addition, neuronal damage scores in the cortex were significantly reduced by HBO for 1 hr and cyclic HBO resuscitation. CONCLUSION: We successfully demonstrated that HBO and, to some extent, hyperbaric air, normobaric hyperoxia, or HBO 8% was found beneficial in resuscitating rats with experimental heatstroke. HBO effectively reduced heatstroke-induced arterial hypotension, hypoxia, plasma tumor necrosis factor-alpha overproduction, and cerebral ischemia and damage and improved survival.     

Efficacy of a T-piece system and a continuous positive airway pressure system for apnea testing in the diagnosis of brain death

OBJECTIVE: To prospectively compare three methods of apnea testing for the confirmation of brain death. DESIGN: Prospective, randomized, crossover study. SETTING: Intensive care unit of a tertiary care university hospital. PATIENTS: Twenty adult patients requiring apnea testing for confirmation of brain death. INTERVENTIONS: Ten minute apnea testing was repeated in random order for every patient with the three oxygenation systems: oxygen catheter inserted through the endotracheal tube (oxygen 6 L/min), T-piece system (oxygen 12 L/min), and continuous positive airway pressure (CPAP) system 10 cm H2O (oxygen 12 L/min). MEASUREMENTS AND MAIN RESULTS: Arterial blood was drawn at 0, 2, 5, and 10 mins of each test. Compared with baseline, Paco2 increased by 30.6 +/- 7.4, 30.0 +/- 7.3 and 30.2 +/- 7.5 mm Hg during the apnea period (p = .96), reaching 73.3 +/- 8.3, 71.6 +/- 11.1, and 72.7 +/- 9.0 mm Hg at the end of the apnea test (p = .73) for the oxygen catheter, the T-piece, and the CPAP, respectively. Pao2 decreased less with the CPAP compared with the oxygen catheter or the T-piece (-22.4 +/- 76, -99.1 +/- 158, and -91.6 +/- 133 mm Hg, respectively, p < .01). In two patients, apnea testing could not be completed with the oxygen catheter and the T-piece because of desaturation, although it could be completed with the CPAP. CONCLUSIONS: The T-piece and the CPAP systems are effective alternatives to the standard oxygen catheter technique for apnea testing. Oxygenation was best maintained with the CPAP system, which can be useful in some patients.     

Importance of hypoxic vasoconstriction in maintaining oxygenation during acute lung injury

OBJECTIVE: To investigate the role of hypoxic pulmonary vasoconstriction in the intrapulmonary blood flow redistribution and gas exchange protection during oleic acid acute lung injury. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Three groups of five mongrel dogs. INTERVENTIONS: Induction of acute lung injury by 0.08 mL/kg oleic acid intravenously. Hypoxic pulmonary vasoconstriction inhibition by Escherichia coli endotoxin microdose (15 microg/kg) pretreatment or by metabolic alkalosis (pH 7.60). MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial and venous resistances were determined by flow-pressure curves and by capillary pressure estimation. Regional lung water and pulmonary blood flow were assessed by positron emission tomography. Oleic acid alone increased the arterial and venous resistances, redistributed blood flow away from edematous areas, and decreased the Pao2 from 507 +/- 16 to 373 +/- 60 torr. on Fio2 1.0 and positive end-expiratory pressure 5 cm H2O. Endotoxin pretreatment inhibited the increase in arterial resistance, suppressed the redistribution, and decreased the Pao2 to 105 +/- 22 torr. Alkalosis inhibited the increase in arterial and venous resistances, suppressed the redistribution, and decreased the Pao2 to 63 +/- 12 torr. Reversal of the alkalosis increased the arterial and venous resistances, restored the perfusion redistribution, and improved the Pao2 to 372 +/- 63 torr. Changes in blood gases conformed to predictions of a computer lung model in which hypoxic pulmonary vasoconstriction was suppressed by endotoxin and alkalosis. CONCLUSIONS: We conclude that in oleic acid-induced lung injury, a) pulmonary hypertension results from increases in both arterial and venous resistances; b) the increase in arterial resistance is the primary mechanism responsible for the perfusion redistribution and the gas exchange protection; and c) the increase in arterial resistance is most consistent with hypoxic pulmonary vasoconstriction.     

Acute graded hypercapnia increases collateral coronary blood flow in a swine model of chronic coronary artery obstruction

OBJECTIVE: To evaluate the effect of acute hypercapnia on regional myocardial blood flow in a swine model of chronic, single-vessel coronary artery obstruction. Permissive hypercapnia is being used frequently in critical care settings. One possible detrimental effect of hypercapnia is the initiation of coronary "steal" in patients with coronary artery disease. The effects of hypercapnia on collateral coronary blood flow in the setting of coronary obstruction have not been defined. DESIGN: Prospective controlled experimental study. SETTING: Institutional animal research facility. SUBJECTS: Eight juvenile swine weighing 25-30 kg. INTERVENTIONS: Collateral coronary circulation was induced in eight piglets by banding the proximal left anterior descending coronary artery for 8-10 wks followed by total ligation. Graded hypercapnia (mean Paco2, 81 torr [10.80 kPa; Paco2 = 81 torr] and 127 torr [16.93 kPa; Paco2 = 127 torr]) was induced by increasing inspiratory carbon dioxide under isoflurane anesthesia (1 minimum alveolar concentration). MEASUREMENTS AND MAIN RESULTS: Animals were attached to instruments to measure pulmonary and systemic hemodynamics, regional myocardial blood flow, and cardiac output. Regional myocardial blood flow was determined using radiolabeled microspheres. Cardiac output, mean arterial pressure, and coronary perfusion pressure were unchanged at both levels of hypercapnia compared with baseline values. Heart rate was increased at Paco2 [HI] (p < .05). Regional blood flow was increased at both levels of hypercapnia in the collateral-dependent and normally perfused myocardium (p < .05; as high as 56% for subendocardium and as high as 106% for subepicardium at Paco2 [HI]). The intercoronary blood flow ratio remained unaltered. The transmural flow ratio was reduced at Paco2 [HI] (P < .05). During hypercapnia, regional lactate extraction remained unaltered, and regional oxygen extraction was unchanged or reduced despite the increase in oxygen consumption. CONCLUSIONS: In this swine model of chronic single-vessel coronary artery obstruction, acute hypercapnia does not induce coronary steal from collateral-dependent myocardium, but it does increase global coronary blood flow.     

Accuracy of mucosal pH and mucosal-arterial carbon dioxide tension for detecting mesenteric hypoperfusion in acute canine endotoxemia

OBJECTIVE: To determine the level of mucosal-arterial Pco2 (Pco2 gap) that is both sensitive and specific for the detection of mesenteric hypoperfusion as defined by either a >50% reduction in portal blood flow or release of lactate by the gut. DESIGN: Animal experiment. SUBJECTS: Seven anesthetized, intubated, mechanically ventilated, and surgically instrumented mongrel dogs. INTERVENTION: Escherichia coli endotoxin (1 mg/kg) given intravenously for 5 mins. MEASUREMENTS AND MAIN RESULTS: Tonometric Pco2, arterial blood gases, arterial and portal venous lactates, and portal and systemic hemodynamic variables were measured. Mucosal pH (pHi) was calculated according to the manufacturers' instructions. From these data, receiver operating characteristics were calculated. Although animals were resuscitated to maintain a constant cardiac output, portal flow decreased from 350+/-101 to 152+/-75 mL/min (p<.01) and the gut released lactate into the portal circulation in all animals. Pco2 gap increased from 13.1+/-3.9 to 40.2+/-39.2 torr (p<.01) and was inversely correlated with portal blood flow (r2 = .20; p<.05). For detection of a >50% reduction in portal blood flow, a Pco2 gap of 20 torr yielded a maximum accuracy of 67% (sensitivity, 55%; specificity, 73%) and was less accurate than a pHi of 7.20, which yielded a maximum accuracy of 76% (sensitivity, 90%; specificity, 70%), although this difference was not significant (p = .24). There was also a correlation between pHi and portal blood flow (r2 = .31; p<.01). For detection of lactate release by the gut, a Pco2 gap of 20 torr was also 67% accurate (sensitivity, 53%; specificity, 78%), whereas a pHi of 7.10 achieved an accuracy of 64% (sensitivity, 40%; specificity, 83%), which was not significantly different. CONCLUSION: Pco2 gap measurements are neither sensitive nor specific for mesenteric hypoperfusion with regard to total gut blood flow reductions of >50% or the release of lactate into the portal circulation.     

Accuracy of intramucosal pH calculated from arterial bicarbonate and the Henderson-Hasselbalch equation: assessment using simulated ischemia

OBJECTIVES: To determine the accuracy of intramucosal pH (pHi) calculated using arterial bicarbonate instead of mucosal capillary bicarbonate in the Henderson-Hasselbalch equation. DESIGN: Simulation of progressive ischemia in mucosal capillary blood. SETTING: University research laboratory. SUBJECTS: Normal human blood diluted with plasma. INTERVENTIONS: Three venous blood specimens were heparinized and diluted to a mean hemoglobin concentration of 5.0 (+/-0.9) g/dL by addition of plasma (2:1, vol:vol). Mucosal capillary aerobic flow stagnation was simulated by multiple exposures of each cooled specimen to a gas mixture containing 90% nitrogen and 10% CO2. When PCO2 measured at 37 degrees C (98.6 degrees F) was approximately 120 torr (16 kPa), the assigned anaerobic threshold, subsequent anaerobic flow stagnation was simulated by mixing the hypercapnic specimens in sealed syringes with five to six successive small aliquots (<100 microL) of lactic acid (10 g/L). MEASUREMENTS AND MAIN RESULTS: The relationship between Pco2 and pH in the specimens was compared with the relationship between the same PCO2 values and pHi calculated by substituting bicarbonate concentrations of 22 and 26 mmol/L in the Henderson-Hasselbalch equation. As PCO2 rose from 50 torr (8 kPa), conventionally calculated pHi increasingly underestimated simulated mucosal capillary pH, with bias >0.1 pH unit at the simulated anaerobic threshold of 120 torr (16 kPa). As PCO2 rose further the values converged, becoming equivalent at PCO2 approximately 150 torr (20 kPa). From PCO2 > or =200 torr (26.7 kPa), conventional pHi progressively overestimated simulated mucosal pH. The difference was >0.3 pH units at PCO2 = 250 torr (33.3 kPa). CONCLUSIONS: In the mucosal PCO2 range usually encountered clinically, the arterial bicarbonate substitution causes underestimation of mucosal capillary pH. With moderate mucosal capillary lactic acidosis the error becomes small, and in severe regional ischemia there is significant overestimation of mucosal capillary pH.     

Small intestine intramucosal PCO(2) and microvascular blood flow during hypoxic and ischemic hypoxia

OBJECTIVE: To determine whether small intestine intramucosal PCO(2) and mucosal blood flow changes would be different between ischemic and hypoxic hypoxia. DESIGN: Randomized animal experiment. SETTING: Research laboratory. SUBJECTS: Anesthetized, mechanically ventilated, and surgically instrumented pigs. INTERVENTIONS: Systemic oxygen delivery was lowered in a stepwise manner to decrease it beyond critical oxygen delivery by lowering either FIO(2) or blood volume. MEASUREMENTS AND MAIN RESULTS: In hypoxic hypoxia pigs (n = 6), arterial oxygen concentration and oxygen delivery decreases were achieved by progressively reducing arterial PO(2) while cardiac index remained unchanged. In ischemic hypoxia pigs (n = 5), oxygen delivery reduction was achieved by progressively reducing cardiac index while arterial PO(2) remained unchanged. In control pigs, oxygen delivery remained unchanged. The lowest oxygen delivery measured in both hypoxia and ischemia experiments was 3.60 +/- 0.26 vs. 2.93 +/- 0.77 mL x kg(-1) x min(-1), respectively (p =.23). At the lowest oxygen delivery level, differences between ischemic hypoxia and hypoxic hypoxia experiments were observed for arterial lactate concentration (468 +/- 308 vs. 1070 +/- 218 mmol/L, respectively; p =.03), mixed venous arterial PCO(2) difference (10 +/- 7 vs. 4 +/- 2 torr, respectively; p =.04), and small intestine mucosal blood flow (6.2 +/- 2.1 vs. 15.7 +/- 7.4 perfusion units, respectively; p =.02). Small intestine intramucosal-arterial difference was higher in ischemic hypoxia than in hypoxic hypoxia (52 +/- 15 vs. 31 +/- 12 torr, respectively; p =.03). CONCLUSION: Small intestine intramucosal PCO(2) increases may indicate systemic oxygen uptake supply limitation in ischemic and hypoxic hypoxia related to conditions of mucosal flow stagnation and CO(2) generation.     

Arterial pH in out-of-hospital cardiac arrest: response time as a determinant of acidosis

It is unclear why some victims of out-of-hospital cardiac arrest are severely acidotic on arrival to the emergency department (ED), whereas others have a pH within normal limits. To explain the difference among patients, the authors collected data on 119 consecutive out-of-hospital adult nontraumatic cardiac arrest victims brought to the University of Nebraska Medical Center by paramedic rescue squad between December 1982 and January 1984. Patients who experienced restoration of spontaneous circulation (ROSC) in the field had a normal pH (7.40 +/- 0.13) as compared with the pH of patients still receiving cardiopulmonary resuscitation (CPR) on arrival at the ED (7.18 +/- 0.20). A rapid paramedic response time was the best determinant of ROSC and a normal pH on arrival at the ED. Bystander CPR neither significantly increased the number of patients with ROSC in the field nor protected against the development of acidosis, but did improve the neurological outcome of survivors. The presence of acidosis in patients still receiving CPR on arrival in the ED could not be predicted on the basis of paramedic response time, amount of sodium bicarbonate given in the field, whether or not the collapse was witnessed, or whether or not bystander CPR had been performed. Patients who were acidotic had a significantly higher (P less than 0.001) Paco2 (101 +/- 33 mm Hg) and a lower Pao2 (41 +/- 69 mm Hg) than patients with a normal pH (Paco2 37 +/- 10 mm Hg, Pao2 134 +/- 107 mm Hg). Adequacy of ventilation is the principal determinant of acidosis in patients who are still receiving CPR on arrival at the ED.     

Hepatic and splanchnic oxygenation during liver transplantation

OBJECTIVE: To evaluate hepatic and splanchnic oxygenation during liver transplantation. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Ten adult patients undergoing liver transplantation. INTERVENTIONS: Standardized surgery and anesthesia without venovenous bypass. MEASUREMENTS AND MAIN RESULTS: Hepatic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in hepatic venous blood. Splanchnic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in portal venous blood and by gastric tonometry. Before reperfusion, the grafts were flushed with 1000 mL of acetated Ringer's solution and 400 mL of portal venous blood. The effluent blood from the graft was wasted and showed a mean pH of 6.86 and a lactate concentration of 9.4 mmol/L. Five minutes after portal reperfusion, most of the grafts produced lactate. Portal-hepatic venous P(CO2) difference ranged from 3 to 16 torr (0.4-2.1 kPa). By the time of restoration of the infrahepatic caval flow mean 24 mins later, eight of the grafts had stopped producing lactate. Mean hepatic venous oxygen tension was 47 torr (6.3 kPa), stabilizing to 41 torr (5.5 kPa) at the end of surgery. Acidosis resolved without pharmacologic interventions. Mean gastric mucosal pH was 7.29 during the anhepatic phase and 7.40 at the end of surgery. One of the patients developed hepatic arterial thrombosis intraoperatively. Her data were analyzed separately. Later, the other patients recovered with good liver function, whereas the patient with hepatic arterial thrombosis was successfully retransplanted. CONCLUSIONS: The liver grafts received well-oxygenated portal venous blood during reperfusion, despite the low values of gastric mucosal pH immediately before reperfusion. Hepatic oxygenation became adequate soon after reperfusion. In the patient with hepatic arterial thrombosis, the recovery of hepatic oxygenation was impaired and lactic acidosis persisted.     

Effect of resuscitative mild hypothermia and oxygen concentration on the survival time during lethal uncontrolled haemorrhagic shock in mechanically ventilated rats.

OBJECTIVE: To test the hypothesis that resuscitative mild hypothermia (MH) (34 degrees C) or breathing fractional inspired oxygen (FIo2) of 1.0 would prolong survival time during lethal uncontrolled haemorrhagic shock (UHS) in mechanically ventilated rats. METHODS: Forty Wistar rats were anaesthetized with halothane, nitrous oxide and oxygen (70/30%), intubated and mechanically ventilated. UHS was induced by volume-controlled blood withdrawal of 3 ml/100 g over 15 min, followed by 75% tail amputation of its length. The animals were randomly divided into four UHS treatment groups (10 rats in each group): group 1 was maintained on an FIo2 of 0.21 and rectal temperature of 37.5 degrees C. Group 2 was maintained on an FIo2 of 0.21 and induced MH. Group 3 was maintained on an FIo2 of 1.0 and 37.5 degrees C. Group 4 was maintained on an FIo2 of 1.0 and MH. Rats were observed otherwise untreated until death. RESULTS: During the initial blood withdrawal, mean arterial pressure (MAP) decreased to 40 mmHg, and the heart rate (HR) increased up to 400 beats/min. The induction of MH increased MAP to 60 mmHg and increased survival time. Moreover, it reduced the HR to 300 beats/min but did not increase bleeding. Ventilation with an FIo2 of 1.0 did not influence MAP, blood loss or survival time, but increased arterial oxygen tension. The mean survival time was 62, 202, 68 and 209 min in groups 1, 2, 3 and 4, respectively. Blood loss from the tail was 1.0, 1.2, 0.9 and 0.7 ml, respectively, in groups 1, 2, 3 and 4. CONCLUSION: MH prolonged the survival time during UHS in mechanically ventilated rats. However, an FIo2 of 1.0 did not influence the survival time or blood loss from the tail.     

Effect of acute hypoxia and hypercapnic acidosis on the development of acetylstrophanthidin-induced arrhythmias

The effect of acutely induced hypoxia, hypercapnic acidosis, and the combination of the two on the amount of acetylstrophanthidin (AS) required to produce cardiac arrhythmias was determined in anesthetized dogs. Each animal was studied during ventilation with room air and again during ventilation with gas mixtures of appropriate concentrations; 24 hr separated the study periods. AS was infused intravenously at a rate of 5 mug/kg per min.Significantly less AS was required to produce arrhythmias during hypoxia and hypercapnic acidosis together than during the period with normal arterial Po(2), Pco(2), and pH (10 animals). Included in this group were two animals which had undergone previous bilateral adrenalectomy and four animals in which heart rate was maintained at the same frequency during both study periods. A significant reduction in the toxic dose of AS also was demonstrated in eight animals, two with constant heart rate, during hypoxia with normal arterial Pco(2) and pH. Hypercapnic acidosis alone (eight animals) did not significantly alter the toxic dose of AS. After the administration of propranolol (six animals) or hexamethionium (six animals), no significant difference was observed between the toxic dose of AS during hypoxia and that during ventilation with room air. Thus although hypoxia and hypercapnic acidosis together do reduce the amount of AS required to produce arrhythmias, it is the hypoxia which exerts the predominant effect on the development of this increased sensitivity to AS. Furthermore, this effect of hypoxia occurs primarily as a result of reflexly augmented sympathetic stimulation of the heart.