Is the combination of nitrous oxide and hyperventilation in elective neurosurgical operations useful?

The use of nitrous oxide (N2O) and hyperventilation (HV) in elective neurosurgery is controversially discussed. The emphasis of the study was to show the effects of N2O and/or moderate hyperventilation (paCO2 31.0 +/- 1.2 mmHg) on parameters of cerebral metabolism: jugularvenous oxygen saturation (SjVO2), cerebral extraction of oxygen (CEO2), arterial jugularvenous difference of oxygen contents (AJDO2), arterial jugularvenous difference of lactate (AJDL) and glucose (AJDGL) and lactate-oxygen index (LOI). The study was approved by the Ethics Committee of the University of Leipzig. Forty patients undergoing an elective craniotomy for brain tumour resection were divided into four groups: group 1: n = 10, N2O + normoventilation (NV), group 2: n = 10, N2O + hyperventilation (HV), group 3: n = 10, O2/air + NV, group 4: n = 10, O2/air + HV. N2O + HV led to a significant decrease in SjVO2 from 68.1 +/- 10.7% to 49.7 +/- 5.6%. O2/Air + HV produced a drop from 67.1 +/- 11.1% to 49.8 +/- 7.7%. CEO2 increased significantly in the group N2O + HV from 30.6 +/- 10.6% to 49.6 +/- 5.5% and in the group O2/Air + HV from 31.7 +/- 11.1% to 50.0 +/- 7.8%. AJDO2 increased significantly in the group N2O + HV from 5.79 +/- 1.54 ml% to maximal 8.49 +/- 1.10 ml% and in the group O2/Air + HV from 5.29 +/- 1.76 ml% to maximal 8.03 +/- 1.76 ml%. In the normoventilation-groups 1 and 3, no significant changes in SjVO2, CEO2 and AJDO2 were observed between MP2 and 4. The parameters AJDL, AJDGL and LOI did not show any significant changes in any of the four groups. The described data represent a reduction of cerebral oxygenation, but deleterious effects caused by cerebral ischaemia could not be observed. Based on our data, hyperventilation and its combination with N2O should not be used routinely in neuroanaesthesia.     

Hyperventilation impairs brain function in acute cerebral air embolism in pigs

OBJECTIVE: To evaluate, in a model of cerebral air embolism (CAE), the effects of ventilation-induced hypocapnia and hyperoxemia on intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain oxygen (PbrO(2)), brain carbon dioxide (PbrCO(2)), brain pH (brpH) and levels of brain glucose and lactate. DESIGN AND SETTING: Prospective animal study in a university medical center. SUBJECTS: Fifteen Landrace/Yorkshire pigs. INTERVENTIONS: In 15 anesthetized pigs ICP, PbrO(2), PbrCO(2) and brpH were measured with multi-parameter sensors, and brain glucose and lactate by microdialysis. All these parameters were recorded for 2 h after injection of air into the internal carotid artery. Nine animals were hyperventilated (PaCO(2 )+/-25 mmHg) and hyperoxygenated (FiO(2) 1.0) and six animals were normoventilated (PaCO(2)()+/-40 mmHg with an FiO(2) 0.4) and served as controls. RESULTS. In the treatment group the ICP rose from 8+/-1 to 52+/-6 mmHg, which was similar to that in the control group (12+/-1 to 57+/-8 mmHg). At the end of the 2-h study period, there were no significant differences in PbrO(2), PbrCO(2) and brpH between the two groups. The decreased brain glucose and increased brain lactate reached severe pathological values in both groups by the end of the 2-h study period. CONCLUSIONS: Hypocapnia and hyperoxemia in acute CAE did not improve pathological functional brain parameters compared with normoventilated controls. Similarly, the pathological changes in brain glucose/lactate could also not be improved by hypocapnia and hyperoxemia.     

Transconjunctival oxygen monitoring as a predictor of hypoxemia during helicopter transport

As the use of helicopters for air transport of critically ill patients increases, the availability of monitoring devices for physiological parameters during flight becomes important. It has long been known that arterial PO2 (PaO2) decreases during unsupplemented, non-pressurized flight. In this study, the authors examined the use of the transconjunctival oxygen (cjO2) monitor for assessing the adequacy of arterial oxygenation during helicopter flight in four healthy volunteers. Arterial PaO2 as measured by conventional blood gas analysis was compared with cjO2 at ground level, 5,000 feet, and 10,000 feet altitude. Mean PaO2 dropped significantly from 93.5 to 81.5 to 58.5 mm Hg, respectively (P less than 0.001, analysis of variance with repeated measures). Mean cjO2 also decreased significantly from 63.8 to 52.0 to 34.8 mm Hg, respectively (P less than 0.001, analysis of variance with repeated measures). Within individual subjects, cjO2 was an accurate predictor of PaO2 (P less than 0.001, multiple regression analysis). The relationship between cjO2 and PaO2 was linear with a regression coefficient of 1.147. The authors conclude that the transconjunctival O2 monitor may be useful for monitoring the adequacy of arterial oxygenation during helicopter flight in hemodynamically stable patients. The results of study also support the use of supplemental oxygen in all patients subjected to helicopter transport.     

Local metabolic effects of dopexamine on the intestine during mesenteric hypoperfusion

This self-controlled experimental study was designed to test the hypothesis that dopexamine, a synthetic catecholamine that activates dopaminergic (DA-1) and beta2-adrenergic receptors, improves oxygenation in the jejunal mucosa during intestinal hypotension. In six normoventilated barbiturate-anesthetized pigs, controlled reductions in superior mesenteric arterial pressure (PSMA) was obtained by an adjustable clamp around the artery. Dopexamine infusions (0.5 and 1.0 microg.kg(-1).min(-1)) were administered at a freely variable PSMA (i.e., with the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. We continuously measured superior mesenteric venous blood flow (QMES; transit-time ultrasonic flowmetry), jejunal mucosal perfusion (laser Doppler flowmetry), and tissue oxygen tension (PO2TISSUE; microoximetry). Jejunal luminal microdialysate of lactate, pyruvate, and glucose were measured every 5 min. Measurements of mucosal PCO2 (air tonometry), together with blood sampling and end-tidal PCO2 measurements, enabled calculations of pHi and PCO2 gap. Dopexamine reduced mesenteric vascular resistance and increased QMES at a PSMA of 50 mmHg and 30 mmHg. At a PSMA of 30 mmHg, dopexamine increased mesenteric oxygen delivery but did not influence mesenteric oxygen uptake or extraction. In this situation, dopexamine had no beneficial effect on jejunal mucosal blood flow. On the contrary, dopexamine increased mesenteric net lactate production and PCO2 gap, whereas PO2TISSUE and pHi decreased. Jejunal luminal microdialysate data demonstrated an increased lactate concentration and a pattern of decreased glucose concentration and increased luminal lactate-pyruvate ratio. These negative metabolic effects of dopexamine should be taken into account in situations of low perfusion pressures.     

Normoxic ventilation during resuscitation and outcome from asphyxial cardiac arrest in rats

The formation of reactive oxygen species during reperfusion is one trigger for neuronal injury after global cerebral ischemia. Because formation of reactive oxygen species requires delivery of molecular oxygen to ischemic tissue, restricting inspired oxygen during reperfusion may decrease neurological damage. This study examined whether ventilation with room air rather than pure oxygen during resuscitation would improve neurological recovery after cardiac arrest in rats. Adult, male rats were subjected to 8 min of asphyxia resulting in cardiac arrest. During resuscitation, rats were ventilated either with hyperoxia (FiO2 = 1.0) or normoxia (FiO2 = 0.21, room air). Neurobehavioral deficits were scored daily for 72 h after resuscitation, after which brains were collected for histology. Normoxia decreased arterial oxygen content. Other physiological parameters and mortality did not differ between groups. All surviving rats exhibited behavioral and histological signs of brain damage. Neurological deficit scores did not differ between normoxia and hyperoxia conditions at any time point. The number of ischemic neurons in the hippocampus also did not differ between groups. These data indicate neither benefit nor detriment of reducing inspired oxygen concentration during resuscitation from asphyxial cardiac arrest in rats.     

Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock

OBJECTIVE: To investigate the impact of exogenous beta-adrenergic receptor stimulation on splanchnic blood flow, oxygen kinetics, glucose-precursor flux, and liver metabolism in septic shock. DESIGN: Prospective trial. SETTING: University hospital intensive care unit. PATIENTS: Six patients with hyperdynamic (cardiac index >4.0 L/min/m2) septic shock, all requiring norepinephrine to maintain blood pressure >65 mm Hg. INTERVENTIONS: We compared norepinephrine and phenylephrine titrated to achieve similar systemic hemodynamics and gas exchange. Splanchnic hemodynamics, oxygen kinetics, and metabolic parameters were measured before, during, and after replacing norepinephrine with phenylephrine. MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow and oxygen kinetics were derived from the steady-state indocyanine-green clearance based on hepatic dye extraction and arterial and hepatic venous blood gases. Endogenous glucose production rate was derived from the plasma appearance rate of stable-isotope-labeled glucose using a primed-constant infusion. Splanchnic lactate, alanine (high-performance liquid chromatography) uptake, and hepatic monoethylglycinexylidide (MEGX) (fluorescence polarization immunoassay) formation rates were calculated from splanchnic blood flow and arterial-hepatic venous concentration differences. Replacing norepinephrine with phenylephrine induced no change in systemic hemodynamics or gas exchange. While splanchnic oxygen consumption and alanine uptake rate remained unaffected, splanchnic blood flow, oxygen delivery, and lactate uptake rate were significantly decreased. Glucose production rate also decreased significantly. A return to norepinephrine restored splanchnic blood flow, oxygen delivery, and lactate uptake rate to baseline values, while glucose production rate remained depressed. Hepatic MEGX formation rate was not influenced during the investigation. CONCLUSIONS: Exogenous beta-adrenergic receptor stimulation determines splanchnic blood flow, oxygen delivery, and glucose precursor flux but not splanchnic oxygen utilization in septic shock. Gluconeogenesis is not directly affiliated to hepatosplanchnic oxygen kinetics. The different response of glucose and MEGX production rates, metabolic pathways of the periportal and perivenous region, may document intrahepatic heterogeneity associated with hepatocellular metabolic compartmentation.     

Effects of increased oxygen breathing in a volume controlled hemorrhagic shock outcome model in rats

It is believed that victims of traumatic hemorrhagic shock (HS) benefit from breathing 100% O(2). Supplying bottled O(2) for military and civilian first aid is difficult and expensive. We tested the hypothesis that increased FiO(2) both during severe volume-controlled HS and after resuscitation in rats would: (1) increase blood pressure; (2) mitigate visceral dysoxia and thereby prevent post-shock multiple organ failure; and (3) increase survival time and rate. Thirty rats, under light anesthesia with halothane (0. 5% throughout), with spontaneous breathing of air, underwent blood withdrawal of 3 ml/100 g over 15 min. After HS phase I of 60 min, resuscitation phase II of 180 min with normotensive intravenous fluid resuscitation (shed blood plus lactated Ringer's solution), was followed by an observation phase III to 72 h and necropsy. Rats were randomly divided into three groups of ten rats each: group 1 with FiO(2) 0.21 (air) throughout; group 2 with FiO(2) 0.5; and group 3 with FiO(2) 1.0, from HS 15 min to the end of phase II. Visceral dysoxia was monitored during phases I and II in terms of liver and gut surface PCO(2) increase. The main outcome variables were survival time and rate. PaO(2) values at the end of HS averaged 88 mmHg with FiO(2) 0.21; 217 with FiO(2) 0.5; and 348 with FiO(2) 1. 0 (P<0.001). During HS phase I, FiO(2) 0.5 increased mean arterial pressure (MAP) (NS) and kept arterial lactate lower (P<0.05), compared with FiO(2) 0.21 or 1.0. During phase II, FiO(2) 0.5 and 1. 0 increased MAP compared with FiO(2) 0.21 (P<0.01). Heart rate was transiently slower during phases I and II in oxygen groups 2 and 3, compared with air group 1 (P<0.05). During HS, FiO(2) 0.5 and 1.0 mitigated visceral dysoxia (tissue PCO(2) rise) transiently, compared with FiO(2) 0.21 (P<0.05). Survival time (by life table analysis) was longer after FiO(2) 0.5 than after FiO(2) 0.21 (P<0. 05) or 1.0 (NS), without a significant difference between FiO(2) 0. 21 and 1.0. Survival rate to 72 h was achieved by two of ten rats in FiO(2) 0.21 group 1, by four of ten rats in FiO(2) 0.5 group 2 (NS); and by four of ten rats of FiO(2) 1.0 group 3 (NS). In late deaths macroscopic necroses of the small intestine were less frequent in FiO(2) 0.5 group 2. We conclude that in rats, in the absence of hypoxemia, increasing FiO(2) from 0.21 to 0.5 or 1.0 does not increase the chance to achieve long-term survival. Breathing FiO(2) 0.5, however, might increase survival time in untreated HS, as it can mitigate hypotension, lactacidemia and visceral dysoxia.     

Biochemical tissue monitoring during hypoxia and reoxygenation

Oxygen deficiency during critical illness may cause profound changes in cellular metabolism and subsequent tissue and organ dysfunction. Clinical treatment in these cases targets rapid reoxygenation to avoid a prolonged impaired synthesis of cellular high-energy phosphates (ATP). However, the effect of this therapeutic intervention on tissue metabolism has not been determined yet. Thus the present study was designed to determine the effects of hypoxia and reoxygenation with either room air or 100% oxygen on variables of interstitial metabolism in different tissues using in vivo microdialysis. Twenty-seven adult, male CD-rats (407-487 g; Ivanovas, Kisslegg, Germany) were studied during general anesthesia. Following preparation and randomization, rats were normoventilated for 45 min (FiO(2) 0.21), followed by induction of hypoxia (FiO(2) 0.1, 40 min) and reoxygenated for 50 min either with FiO(2) 1.0 (group 1, n=10) or FiO(2) 0.21 (group 2, n=10). Control animals (n=7) were ventilated with 21% oxygen during the observation period. Additional to invasive haemodynamic parameters, biochemical tissue monitoring was performed using CMA 20 microdialysis probes, inserted into muscle, subcutaneous space, liver, and the peritoneal cavity allowing analyses of lactate and pyruvate at short intervals. Hypoxia induced a significant reduction in mean arterial pressure (MAP) in group 1 and 2 compared with the control group (P<0.05) without any significant differences between both treatment groups. This was accompanied by a significant increase in blood lactate (10.5+/-3.1 mM (group 1) and 12.3+/-4.1 mM (group 2) vs. 1.5+/-0.3 mM (control); P<0.05) and severe metabolic acidosis (base excess (BE): -18.3+/-5 mM (1) and -17.3+/-7 mM (2) vs. -2.6+/-1.8 mM (control), P<0.05). During hypoxia, the interstitial lacate/pyruvate ratio in groups 1 and 2 increased to 455+/-199% (muscle), 468+/-148% (intraperitoneal), 770+/-218% (hepatic) and 855+/-432% (subcutaneous) (P<0.05 vs. control, respectively). No significant inter-organ or inter-group differences in interstitial dialysates were observed in the treatment groups, neither during hypoxia nor during reoxygenation. Our data suggest, that hypoxia induces comparable metabolic alterations in various tissues and that reoxygenation with 100% oxygen is not superior to 21% oxygen in restoring tissue metabolism after critical hypoxia.     

Mechanisms of Seizures and Coma in Hypoglycemia EVIDENCE FOR A DIRECT EFFECT OF INSULIN ON ELECTROLYTE TRANSPORT IN BRAIN

The mechanisms involved in the production of hypoglycemic coma were studied in rabbits. Measurements were made in brain, cerebrospinal fluid (CSF), and plasma of osmolality, Na(+), K(+), Cl(-), water content, exogenous insulin, glucose, lactate, and glutamate, while pH, Pco(2), Po(2), and bicarbonate were evaluated in arterial blood, 35 min after i.v. injection of insulin (50 U/kg), plasma glucose did not change, but brain K(+) content increased significantly. Grand mal seizures were observed in unanesthetized animals (+/-SD) 133+/-37 min after administration of insulin, at a time when brain glucose was normal, but brain tissue content of Na(+), K(+), osmoles, and water was significantly greater than normal. Coma supervened 212+/-54 min after insulin injection, at which time brain glucose, lactate, and glutamate were significantly decreased. At both 35 and 146 min after insulin administration, exogenous insulin was present in brain, but not in the CSF. After 208 min of insulin administration, animals were given i.v. glucose and sacrificed 35 min later. Most changes in the brain produced by hypoglycemia were reversed by the administration of glucose. Hypoxia (Po(2) = 23 mm Hg) was produced and maintained for 35 min in another group of animals. Hypoxia caused brain edema but did not affect brain electrolyte content. However, brain lactate concentration was significantly greater than normal. The data indicate that the seizures noted early in the course of insulin-induced hypoglycemia are temporally related to a rise in brain osmolality secondary to an increased net transport into brain of Na(+) and K(+), probably caused by insulin, per se. As hypoglycemia persists, there is also depletion of energy-supplying substrates (glucose, lactate, glutamate) in the brain, an event which coincides with the onset of coma. The brain edema observed during hypoxia is largely due to an increase in brain osmolality secondary to accumulation of lactate.     

The influence of normobaric hyperoxia on hepatic oxygenation--experience with an animal model

We investigated the effect of a ventilation with an FiO2 of 1.0 on arterial and hepatic venous oxygenation in 23 G?ttingen minipigs. Under balanced anaesthesia (isoflurane/fentanyl), a fibreoptic catheter was placed into a hepatic vein. The correct position of the tip of the catheter was controlled manually after laparotomy. After measurement of baseline values (arterial and hepatic blood gases, ShvO2), in 13 minipigs normoventilation with an FiO2 of 1.0 was performed for 15 minutes. Thereafter, ventilation was continued with an FiO2 of 0.4. In the control group (n = 10), the animals were oxygenated with an FiO2 of 0.4 permanently. The changes due to hyperoxia were measured in hepatic venous oxygen saturation (ShvbgaO2: from 81.2 +/- 1.43% to 87.5 +/- 1.77%, ShvoximO2: from 82.6 +/- 1.14% to 90.5 +/- 0.90%), arterial (from 217.5 +/- 5.0 mmHg to 467.2 +/- 22.0 mmHg) and hepatic venous (from 51.8 +/- 2.0 mmHg) oxygen partial pressure. We found a correlation between hepatic venous oxygen partial pressure und ShvbgaO2 in the blood (r = 0.84, p < 0.001) and between ShvO2 (ShvbgaO2/ShvoximO2), which was either measured directly in the blood or by a fibreoptic catheter (r = 0.6, p < 0.001). Whereas the increase in ShvO2 during hyperoxia may be a result of increased arterial supply, the decrease in ShvO2 after the end of hyperoxia below baseline values needs further investigations. The continuous fibreoptic measurement of ShvoximO2, also under hyperoxic conditions is a valuable parameter for the monitoring of hepatic venous oxygenation.     

The relationship between extravascular lung water and oxygenation in three patients with influenza A (H1N1)-induced respiratory failure

This case series reports the correlation between extravascular lung water (EVLW) and the partial arterial oxygen pressure/fractional inspiratory oxygen (PaO(2)/FiO(2)) ratio in three patients with severe influenza A (H1N1)-induced respiratory failure. All patients suffered from grave hypoxia (PaO(2), 26-42 mmHg) and were mechanically ventilated using biphasic airway pressure (PEEP, 12-15 mmHg; FiO(2), 0.8-1) in combination with prone positioning at 12 hourly intervals. All patients were monitored using the PICCO system for 8-11 days. During mechanical ventilation, a total of 62 simultaneous determinations of the PaO(2)/FiO(2) ratio and EVLW were performed. A significant correlation between EVLW and the PaO(2)/FiO(2) ratio (Spearman-rho correlation coefficient, -0.852; p < 0.001) was observed. In all patients, a decrease in EVLW was accompanied by an improvement in oxygenation. Serum lactate dehydrogenase levels were elevated in all patients and significantly correlated with EVLW during the intensive care unit stay (Spearman-rho correlation coefficient, 0.786; p < 0.001). In conclusion, EVLW seems increased in patients with severe H1N1-induced respiratory failure and appears to be closely correlated with impairments of oxygenatory function.     

体外循环心内直视手术复温期病人脑氧合及氧代谢对颅内血浆S-100蛋白水平的影响

目的通过分析体外循环心内直视手术复温期病人脑氧合及氧代谢指标对颅内血浆S-100蛋白水平的影响,找到影响体外循环心内直视手术后病人脑损伤程度的权重指标,从而更好地预防和/或减少体外循环心内直视手术后病人神经系统并发症。方法择期心内直视手术病人22例,在CPB复温到36℃时采集颈内静脉球部血液检测S-100蛋白水平,并计算得出脑氧合及氧代谢指标;用多因素线性回归分析模型评价各脑氧合及氧代谢指标对颅内血浆S-100蛋白水平的影响。结果影响体外循环心内直视手术复温期病人颅内血浆S-100蛋白水平的权重指标包括脑葡萄糖摄取率、脑氧摄取率和脑乳酸氧指数。结论在体外循环心内直视手术的临床监测指标中脑葡萄糖摄取率、脑氧摄取率和脑乳酸氧指数与术后神经系统并发症的发生高度相关。     

Transcutaneous pressure of oxygen: a noninvasive and early detector of peripheral shock and outcome

A noninvasive tool to recognize early shock would improve outcome by providing prompt recognition of tissue ischemia and precise resuscitation endpoint. The skin is the first tissue bed to vasoconstrict in shock states. Studies have demonstrated that transcutaneous partial pressure of oxygen (PtCO2) increases with higher FiO2 in nonshock states as arterial pressure of oxygen (PaO2) increases, but in shock situations, PtCO2 mirrors changes in cardiac output and oxygen delivery with minimum response to increasing FiO2 and PaO2. This study examined the relationship of hemodynamic variables and the degree of PtCO2 response to FiO2 of 1.0 (identified as the "oxygen challenge test") to mortality and organ failure. This prospective observational study examined 38 patients requiring at least 24 h of cardiac output monitoring for shock resuscitation in the Surgical Intensive Care Unit. Patients were resuscitated to the standard protocol of blood pressure, urine output, oxygen delivery (DO2), and mixed venous O2 (SvO2). Seventy-nine percent of the patients (30/38) with a mean age of 59 +/- 21 years had septic shock or severe sepsis with a 26% mortality (10/38). Measurements included hemodynamic variables, PtCO2, and outcome (mortality and organ failure). In this study, the ability of PtCO2 value to increase by 21 mmHg on a FiO2 of 1.0, at 24 h of resuscitation, divided survivors from nonsurvivors, P <.001. The PtCO2 response to FiO2 may provide an additional noninvasive method of detecting early shock as well as a specific endpoint of resuscitation.     

Brain glucose and lactate levels during ventilator-induced hypo- and hypercapnia

OBJECTIVE: Levels of glucose and lactate were measured in the brain by means of microdialysis in order to evaluate the effects of ventilator-induced hypocapnia and hypercapnia on brain metabolism in healthy non-brain-traumatized animals. DESIGN AND SETTING: Prospective animal study in a university laboratory. SUBJECTS: Eight adult Landrace/Yorkshire pigs. INTERVENTIONS: The microdialysis probe was inserted in the brain along with a multiparameter sensor and intracranial pressure (ICP) probe. The animals were ventilated in a pressure-controlled mode according to the open lung concept with an inspired oxygen fraction of 0.4/1.0. Starting at normoventilation (PaCO(2) +/-40 mmHg) two steps of both hypercapnia (PCO(2) +/- 70 and 100 mmHg) and hypocapnia (PaCO(2) +/- 20 and 30 mmHg) were performed. Under these conditions, brain glucose and lactate levels as well as brain oxygen (PbrO(2)), brain carbon dioxide (PbrCO(2)), brain pH (brpH), brain temperature and ICP were measured. RESULTS: At hypercapnia (PaCO(2) = 102.7 mmHg) there were no significant changes in brain glucose and lactate but there was a significant increase in PbrCO(2), PbrO(2) and ICP. In contrast, at hypocapnia (PCO(2) = 19.8 mmHg) there was a significant increase in brain lactate and a significant decrease in both brain glucose and PbrCO(2). CONCLUSIONS: Hypocapnia decreases brain glucose and increases brain lactate concentration, indicating anaerobic metabolism, whereas hypercapnia has no influence on levels of brain glucose and brain lactate.     

Effect of dopexamine on hepatic metabolic activity in patients with septic shock

Hepato-splanchnic metabolic activity is seen to be related to regional blood flow and oxygen/substrate availability in patients with sepsis. Catecholamines, which may modulate metabolic activity perse, are common to stabilize hemodynamics. We studied the effect of a dopexamine-induced increase in splanchnic blood flow (Qspl) on regional metabolic rate in 10 patients with septic shock requiring norepinephrine to maintain mean arterial pressure (>60 mmHg). Splanchnic blood flow was determined using the indocyanine-green method with hepatic venous sampling. We determined the hepato-splanchnic lactate, pyruvate, alanine, and glutamine turnover and the lactate/pyruvate and ketone body ratio as well as the endogenous glucose production (EGP) using the stable isotope approach. Qspl increased from 0.86 (0.79-1.15) to 0.96 (0.92-1.33) L/min/m2, not influencing any parameter of metabolic activity. We speculate that this finding is due to altered beta-adrenoreceptor-mediated thermogenic effects due to the interplay of different beta-sympathomimetics at the receptor site.     

Leg blood flow and muscle metabolism in occlusive arterial disease of the leg before and after reconstructive surgery.

1. Leg blood flow, uptake of oxygen and glucose and release of lactate by the leg and changes in intramuscular concentrations of metabolites were studied at rest and during exercise of increasing work loads in thirteen patients with occlusive disease of the iliac or superficial femoral arteries. 2. Leg blood flow (dye-dilution technique) and oxygen uptake during exercise were low and levelled with increasing work load. Considerable increases were noted in muscle lactate concentration and in the net release of lactate from the exercising leg. Muscle content (needle-biopsy technique) of ATP and creatine phosphate decreased during exercise, with an almost complete depletion of creatine phosphate in three patients. The decrease in muscle glycogen during work did not differ significantly from that of control subjects. 3. Repeated exercise after reconstructive surgery showed a considerable improvement in physical working capacity. Leg blood flow and oxygen uptake during exercise were significantly higher than before surgery and increased linearly in relation to work intensity. The decrease in creatine phosphate and lactate concentration of the thigh muscle during exercise was less pronounced and the release of lactate was lower than before vascular reconstruction. 4. It is suggested that the onset of the severe muscle symptoms during exercise in patients with occlusive arterial disease of the leg may be related to a low concentration of ATP and creatine phosphate in the affected muscles.     

Brain protection in open heart surgery in patients with infective endocarditis

Effect of nimotope on cerebral metabolism and incidence of mental disorders in patients operated on under forced ventilation of the lungs (FVL) was studied in 32 patients subjected to replacement of mitral and aortic valves for infective endocarditis. Nimotope was used for preventing hypoxic disorders of the CNS. The drug was injected starting from the stage of operation before FVL. Cerebral hypoxia was diagnosed using lactate-oxygen index (LOI) and other cerebral metabolic coefficients. LOI increased in all patients immediately after FVL, being much higher in the patients without cerebral protection. Moreover, numerous neurotic and mental disorders were observed in this group of patients during the early postoperative period. By contrast, no mental disorders, disorders of memory or attention were detected in the patients treated with nimotope. These data indicate that nimotope decreases the unfavorable effect of FVL on the CNS function in patients with infective endocarditis. The difference of lactate content in arterial blood and in the internal jugular vein bulb and LOI can be used for the diagnosis of brain ischemia in heart surgery with FVL.     

Effects of the correction of renal anaemia by erythropoietin on physiological changes during exercise

Abstract. The effects of treating the anaemia of end-stage renal failure with erythropoietin were studied in nine dialysis patients. The increase in haemoglobin concentration (by 59% from 7.0 ± 1.2 to 11.1 ± 1.1 g dl^-1) was associated with increases in exercise duration (by 41%) and maximum oxygen consumption (by 34%). Treatment reduced resting heart rate but did not significantly alter heart rate at maximum exercise, nor resting or exercise blood pressure. Resting arterial potassium concentrations were slightly increased after treatment, but they increased similarly in relation to minute ventilation during exercise. Lactic acidaemia developed during exercise at both levels of haemoglobin, and was accompanied by similar reductions in arterial pH and bicarbonate levels but constant Pao₂ and Paco₂. Ventilation was coupled to the metabolic rate of carbon dioxide production, ventilatory dead-space and arterial Pco₂ before and after treatment of anaemia, the ventilatory requirement for carbon dioxide elimination being unchanged. Treatment of anaemia did not alter resting arterial lactate concentration; the concentration of lactate at maximum exercise was increased slightly following treatment but this increase did not reach statistical significance. The rate of increase in arterial lactate concentration as a function of oxygen consumption, assessed both with respect to the 'lactate threshold' and 'lactate slope index', was significantly delayed by treatment. Treatment of anaemia also delayed the 'anaerobic threshold', and there was good correlation between lactate and anaerobic thresholds. Treatment of renal anaemia by erythropoietin thus results in improved tissue oxygen supply during exercise, reflected by delay in the onset of lactic acidaemia.     

Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study

OBJECTIVE: To determine whether correction of acidemia using bicarbonate improves hemodynamic variables and tissue oxygenation in patients with lactic acidosis. DESIGN: Prospective, randomized, blinded, cross over study. Each patient sequentially received sodium bicarbonate and sodium chloride. The order of the infusions was randomized. PATIENTS: Ten patients with metabolic acidosis, increased arterial plasma lactate concentrations (greater than 2.45 mmol/L), and no severe renal failure (creatinine less than 250 mumol/L [less than 2.3 mg/dL]). METHOD: Sodium bicarbonate (1 mmol/kg body weight) or equal volume of sodium chloride was injected iv at the beginning of two successive 1-hr study periods. Period order was randomized. Arterial and venous blood gas measurements, plasma electrolytes (sodium, potassium, chloride), osmolality and lactate, 2,3-diphosphoglycerate (DPG), and oxygen hemoglobin affinity, hemodynamic variables, oxygen delivery, and oxygen consumption measurements were obtained before and repeatedly during the 1-hr period after the injection of bicarbonate or sodium chloride. MEASUREMENTS AND MAIN RESULTS: Sodium bicarbonate administration increased arterial and venous pH, serum bicarbonate, and the partial pressure of CO2 in arterial and venous blood. Hemodynamic responses to sodium bicarbonate and sodium chloride were similar. Tissue oxygenation (as estimated by oxygen delivery, oxygen consumption, oxygen extraction ratio, and transcutaneous oxygen pressure) was not modified. No changes in serum sodium concentration, osmolality, arterial and venous lactate, red cell 2,3-DPG levels, or hemoglobin affinity for oxygen were observed. CONCLUSION: Administration of sodium bicarbonate did not improve hemodynamic variables in patients with lactic acidosis, but did not worsen tissue oxygenation.     

Surfactant therapy for acute respiratory distress in severe pediatric burn injury: a case series

After severe burn injury, pediatric patients often succumb to complications of respiratory failure. Surfactant has been used to improve pulmonary gas exchange for severe respiratory distress in other pediatric populations but has not been studied in pediatric burn-injured patients. Here, the authors report a case series of seven severely burned pediatric patients who received surfactant for acute respiratory distress and severe hypoxemia. Seven cases were reviewed of pediatric patients who received surfactant for severe acute respiratory distress. Data analyzed included age, TBSA burned, height, weight, mechanism of injury, total intensive care unit days, hospital days, and ventilator days. Modes of ventilation, peak inspiratory pressure, oxygen requirement, arterial blood gas analysis, blood pressure, and heart rate were analyzed before and the day following surfactant therapy. Four patients had reduced oxygen requirements following surfactant administration (FiO(2): 0.66 ± 0.23-0.48 ± 0.025). Three patients showed no reduction in oxygen requirements (FiO(2): 0.95 ± 0.09-0.90 ± 0.0). The remaining four patients who had reduced oxygen requirements received surfactant earlier following their injury (4.8 ± 0.9 days postinjury vs 17.7 ± 8 days postinjury) and had less derangement in oxygenation before surfactant dosing (PaO(2):FiO(2) ratio: 105.2 ± 26.4 vs 64.5 ± 5.2). Surfactant therapy may offer a therapeutic option during acute respiratory distress for severely burned pediatric patients. Surfactant may be useful early in the course of severe hypoxemia and acute respiratory distress but may not be effective as a salvage modality.