Randomized trial of low versus high carbon dioxide insufflation pressures in posterior retroperitoneoscopic adrenalectomy

Background

Posterior retroperitoneoscopic adrenalectomy has gained widespread acceptance for the removal of benign adrenal tumors. Higher insufflation pressures using carbon dioxide (CO₂) are required, although the ideal starting pressure is unclear. This prospective, randomized, single-blinded, study aims to compare physiologic differences with 2 different CO₂ insufflation pressures during posterior retroperitoneoscopic adrenalectomy.

Respiration: control of ventilation

Ventilation of the lungs is tightly regulated to maintain a P_aCO₂ that supports optimal acid-base status and an adequate PaO₂. Central and peripheral chemoreceptors feed into respiratory control centres in the brainstem. P_aO₂ exerts its influence mainly through peripheral chemoreceptors, whereas P_aCO₂ exerts its influence mainly through the central chemoreceptors and, to a much lesser extent, the peripheral chemoreceptors. The tightest physiologic control is over P_aCO₂. Indeed, a linear relationship exists between P_aCO₂ and alveolar ventilation through a broad range of P_aCO₂ values. In contrast, for P_aO₂, significant stimulation of respiration only occurs at low levels (approximately 8 kPa or less). The combination of hypoxaemia and hypercarbia exerts a synergistic effect on promoting ventilation. Acidosis, whether respiratory or metabolic, is also a potent stimulus for ventilation. Other influences on ventilatory control include airway reflexes to inhaled toxins. Various drugs used in anaesthesia and critical care medicine depress ventilation, most markedly opioids, while others notably caffeine are used to stimulate it. Evidence of disordered control of ventilation is seen in some disease states, the phenomenon of Cheyne-Stokes respiration being particularly well recognized. Measurement of respiratory drive is increasingly used in intensive care to individualize mechanical ventilation.     

Distal renal tubular acidosis: the value of urinary pH,PCO2 and NH4 + measurements

Distal renal tubular acidosis (dRTA) is not a single disease. The experimental forms of the syndrome are unsatisfactory as models of the naturally occurring disease, not least because they are seldom complicated by nephrocalcinosis, which is present in the majority of patients with spontaneous disease and contributes to the renal tubular defects found in the syndrome. Impairment of minimal urine pH, reduced urine carbon dioxide tension (PCO₂) during passage of alkaline urine, and reduced urinary ammonium (NH₄ ⁺) excretion, have all been advocated as essential criteria for the diagnosis of dRTA. Minimal urine pH, measured during metabolic acidosis, sulphate infusion, or after oral frusemide, is the yardstick against which other criteria should be assessed. A reduced urinaryPCO₂ is commonly found in dRTA but is not specific for the syndrome and may be accounted for by tubular defects other than those involving reduced distal hydrogen ion secretion. NH₄ ⁺ excretion is reduced in most patients with renal acidosis whatever the nature of the underlying renal disease; this function is closely related to nephron mass, and is not specifically impaired in renal tubular disease.     

The syndrome of renal tubular acidosis and nerve deafness. Discordant manifestations in dizygotic twin brothers

The syndrome of renal tubular acidosis (RTA) and nerve deafness is a distinct nosological entity that is inherited as an autosomal recessive trait. We studied a pair of dizygotic twin brothers both with nerve deafness but only one with RTA. Distal RTA was diagnosed in twin A because of inappropriately high urinary pH (6.9) and low net acid excretion (40.0 Eq/min per 1.73 m²) in the presence of hyperchloraemic metablic acidosis, and fractional bicarbonate excretion of 1.6% at a normal serum bicarbonate concentration. The urine minus bloodPCO₂ differences (U-BPCO₂) during a neutral sodium phosphate load and in alkaline urine induced by bicarbonate supplementation were: 11 and 0 mm Hg, respectively. Twin A developed nephrocalcinosis and, after a 9.5-year follow-up period, was 5.3 cm taller than his brother. Twin B remained asymptomatic. Periodic determinations of blood pH and serum bicarbonate were normal and urine pH decreased to 4.6 in the face of ammonium chloride-induced metabolic acidosis. The U-BPCO₂ assessed in alkaline urine was 33.5 mm Hg. Audiograms demonstrated bilateral nerve deafness in both brothers. The presence of deafness without RTA has not been previously reported in this syndrome. This report also shows that a primary distal acidification defect is responsible for the RTA observed in this syndrome.     

Abdominal insufflation with CO<Subscript>2</Subscript> causes peritoneal acidosis independent of systemic pH

We have shown that the inflammation-attenuating effects of CO₂ pneumoperitoneum during laparoscopy are not due to changes in systemic pH. However, acidification of peritoneal macrophages in an in vitro CO₂ environment has been shown to reduce LPS-mediated cytokine release. We tested the hypothesis that the peritoneum is locally acidotic during abdominal insufflation with CO₂deven when systemic pH is corrected. Rats (n = 20) were anesthetized and randomized into two groups: continued spontaneous ventilation (SV) or intubation and mechanical ventilation (MV). All animals were then subjected to abdominal insufflation with CO₂. Mean arterial pH among SV rats decreased significantly from baseline after 15 and 30 minutes of CO₂ pneumoperitoneum (7.329→7.210→7.191, P < 0.05), while arterial pH among MV rats remained relatively constant (7.388→7.245→7.316, P = NS). In contrast, peritoneal pH dropped significantly from baseline and remained low for both groups during CO₂ abdominal insufflation (SV 6.74 → 6.41 → 6.40, P < 0.05; MV 6.94 → 6.45 → 6.45, P < 0.05). In a second experiment, rats (n = 10) were randomized to receive abdominal insufflation with either CO₂ or helium. Abdominal insufflation with helium did not significantly affect peritoneal pH (7.10 → 7.02 →6.95, P = NS), and the decrease in pH among CO₂-insufflated animals was significant compared with helium-insufflated animals (P < 0.05). Peritoneal pH returned to baseline levels in all groups within 15 minutes of desufflation in both experiments. A significant local peritoneal acidosis occurs during laparoscopy which is specifically attributable to the use of CO₂ and which is independent of systemic pH. These data provide additional evidence that localized peritoneal acidosis is central to the mechanism of CO₂-mediated attenuation of the inflammatory response following laparoscopic surgery. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Uniformed Services University, the Department of the Air Force, or the Department of Defense.     

Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia

Background. The pathophysiology of the serotoninergic systemin malignant hyperthermia (MH) is not completely understood.The serotonin-2 (5HT_2A) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropanehydrochloride (DOI) induces typical MH symptoms, including skeletalmuscle rigidity, an increase in body temperature, hyperventilationand acidosis in conscious MH-susceptible (MHS) pigs. Whetherthese symptoms are directly generated in skeletal muscle, resultfrom central serotonergic overstimulation or from a porcinestress syndrome remains unresolved. In this study the in vivoeffects of DOI on anaesthetized (and thus stress-protected)MHS and MH-normal (MHN) pigs were investigated. Methods and results. DOI 1 mg kg^–1 was administered threetimes at 40-min intervals to five MHS and five MHN anaesthetizedpigs. Body temperature, heart rate, muscle tone, arterial carbondioxide pressure (Pa_CO2), pH and creatine kinase concentrationswere measured. The clinical occurrence of MH was defined byPa_CO2 above 70 mm Hg and an increase in body temperature ofmore than 2 °C. Intragroup differences were analysed withthe Friedman test as an overall non-parametric ANOVA and, incase of significance, with the Wilcoxon test. Intergroup comparisonswere performed with the Mann–Whitney U-test (statisticalsignificance P<0.05). MHS and MHN pigs developed muscle fasciculations,significant increases in body temperature and Pa_CO2 and a significantdecrease in pH after the administration of DOI. These changeswere comparable in both groups until the third dose of DOI,when in MHS pigs heart rate and Pa_CO2 rose significantly andpH fell significantly compared with MHN pigs. All MHS pigs fulfilledthe MH criteria. Body temperature increased by more than 2 °Cin all MHN pigs and Pa_CO2 exceeded 70 mm Hg in two. Thus, twoMHN pigs fulfilled the criteria of MH. Conclusions. The comparability of the clinical presentationfollowing DOI administration in MHS and MHN animals and theorder of the development of MH-like symptoms favour the hypothesisof a central serotonergic overstimulation, leading to a serotoninsyndrome. Br J Anaesth 2003; 91: 281–4     

Intraoperative recording of tissue gas tensions in calf muscles of patients with peripheral arterial disease

O₂ and CO₂ tensions were determined in the gastrocnemius muscles of patients undergoing reconstructive arterial surgery due to obstructive arteriosclerosis (32 patients) or abdominal aortic aneurysm (5 patients). Four patients undergoing some other major operation in the abdominal region and showing no signs of arterial ischemia served as controls. Measurements of tissue gas tensions were carried out by means of implanted Silastic tonometers. Immediately after the beginning of operation basal tissue gas tensions showed no essential differences between the various groups of patients: those with (a) intermittent claudication, (b) rest pain, (c) ischemic gangrene, (d) abdominal aortic aneurysm, and (e) controls. Closure of the aorta resulted in a profound fall of muscle PO₂ and elevation of muscle PCO₂. During reactive hyperemia after the release of circulation the tissue PO₂ levels increased sharply and the tissue PCO₂ declined. These changes were clearest in aneurysm patients and smallest in patients with ischemic gangrene. Before closure of wounds local intra-arterial injection of papaverin increased the tissue PO₂ and decreased the PCO₂ for a few minutes. The largest changes were observed in control and aneurysm patients and the smallest in patients with ischemic gangrene. At the end of operations the muscle tissue gas tensions varied according to the severity of the disease, the lowest O₂ tensions and the highest CO₂ levels being observed in the most ischemic extremities. In advanced ischemia the occlusive lesions were frequently multi-segmental in nature and therefore, arterial bypass at one level was not sufficient to normalize tissue oxygenation completely.     

The relationship of glucagon and insulin to sequential changes in metabolic fuel utilization in shock

Previous studies in the dog have demonstrated significant alterations in the mobilization of metabolic fuel during shock. In particular, mobilization of depot fat is markedly depressed. The present study examines the sequential utilization of nonlipid fuels over a 24-hr shock period. Metabolic rates were unchanged from controls. Skeletal muscle glycogen fell exponentially from 7.0 ± 0.5 to 2.7 ± 0.2 mg/g (P < 0.001) after 24 hr of shock. Protein breakdown as reflected by urea production was linear throughout the period and increased 50% over controls (P < 0.001). Lactate levels did not reflect changes in metabolic rate but fell to nearly normal levels once muscle glycogen was depleted. The contribution of CHO and protein combined to CO₂ production fell from 70% in early shock to 42% in the final 12 hr of the 24-hr shock period. This compares to 23% in controls. Protein catabolism alone accounted for an average of 32% of CO₂ production in shock. While insulin levels rose slightly in early shock and then fell, glucagon rose rapidly in the first 5 hr of shock and then remained significantly and constantly elevated throughout the entire shock period. The insulin-glucagon molar ratio remained in the severely catabolic range throughout.     

Helium Pneumoperitoneum Ameliorates Hypercarbia and Acidosis Associated with Carbon Dioxide Insufflation during Laparoscopic Gastric Bypass in Pigs

Background: In the morbidly obese patient undergoing laparoscopic gastric bypass (LGBP), insufflation with carbon dioxide to 20 mmHg for prolonged periods may induce significant hypercarbia and acidosis with attendant sequelae. We hypothesize that the use of helium as an insufflating agent results in less hypercarbia and acidosis. Methods: The study was performed between May and November 2002. A Paratrend 7 fiberoptic probe was placed via a carotid artery catheter in 5 adult Yorkshire swine as continuous pH and pCO₂ levels were measured. Animals were ventilated to a constant pCO₂, after which LGBP was performed. Blood gas values were measured during the procedure and for 1 hour after release of pneumoperitoneum. Helium was used for insufflation in 3 of the pigs and CO₂ in 2. Comparison of arterial pH and pCO₂ were made between groups. Results: Mean maximum pCO₂ for the control group (CO₂ insufflation) was 99.75 ± 22.98 mmHg, while for the experimental group (helium insufflation) was 52.86 ± 6.27mmHg (P=.036). Mean low pH for the groups were 7.10 ± .056 and 7.36 ± .015 (P =.004) respectively. Normalization of pCO₂ in the helium group occurred at a mean of 14.58 min (SD 13.3 min) after release of pneumoperitoneum, while in the control group levels did not normalize (mean final pCO₂= 71.5 mmHg). Conclusions: Helium pneumoperitoneum in LGBP is associated with less intraoperative hypercarbia and acidosis than is the use of CO₂. In addition, pCO₂ returns to normal more rapidly postoperatively with the use of helium insufflation. Study of helium insufflation in humans undergoing LGBP is needed to prove its benefits in the clinical setting.     

Effects of exchange transfusion with liposome-encapsulated hemoglobin on VO₂/DO₂

We clarified the effect of exchange transfusion with liposome‐encapsulated hemoglobin (neo red cells, NRCs) with low O₂ affinity (P₅₀O₂ = 50 mm Hg) on O₂ metabolism. Rabbits were randomly assigned to receive serial exchange transfusions with NRC (NRC group, n = 5), shed blood diluted 1:1 with saline (red blood cell (RBC) group, n = 5), or saline alone (plasma group, n = 4) under hemodynamic monitoring. Cardiac tamponade was then induced and successively reversed to determine relationships between O₂ consumption (VO₂) and O₂ delivery (DO₂) using the dual‐line method. Mean values of Hb concentration after exchange transfusion were 5.7 (NRC), 6.0 (RBC), and 1.5 (plasma) g/dL. The plasma group could not even survive the initial exchange hemodilution due to a critical decrease in DO₂. The NRC, but not the RBC group, developed progressive metabolic acidosis and lactatemia, as well as increases in PaCO₂ and decreases in tissue PO₂ in skeletal muscle after exchange transfusion. Nonetheless, systemic O₂ uptake indices obtained from an analysis of the VO₂/DO₂ relationship in the NRC and RBC groups were comparable. These findings suggested that systemic O₂ uptake was maintained in rabbits after exchange transfusion with NRC, although progressive tissue hypoxia with systemic acidosis is indicative of inadequate peripheral circulation and insufficient aerobic metabolism during extended hemodilution in which 86% of the circulating blood is replaced.     

Pressure-controlled ventilation improves oxygenation during laparoscopic obesity surgery compared with volume-controlled ventilation

Background: We compared pressure and volume-controlled ventilation (PCVand VCV) in morbidly obese patients undergoing laparoscopicgastric banding surgery. Methods: Thirty-six patients, BMI>35 kg m^–2, no major obstructiveor restrictive respiratory disorder, and Pa_CO2<6.0 kPa, wererandomized to receive either VCV or PCV during the surgery.Ventilation settings followed two distinct algorithms aimingto maintain end-tidal CO₂ (E'_CO2) between 4.40 and 4.66 kPaand plateau pressure (P_plateau) as low as possible. Primaryoutcome variable was peroperative P_plateau. Secondary outcomeswere Pa_O2 (FI_O2 at 0.6 in each group) and Pa_CO2 during surgeryand 2 h after extubation. Pressure, flow, and volume time curveswere recorded. Results: There were no significant differences in patient characteristicsand co-morbidity in the two groups. Mean pH, Pa_O2, Sa_O2, andthe Pa_O2/FI_O2 ratio were higher in the PCV group, whereas Pa_CO2and the E'_CO2–Pa_CO2 gradient were lower (all P<0.05).Ventilation variables, including plateau and mean airway pressures,anaesthesia-related variables, and postoperative cardiovascularvariables, blood gases, and morphine requirements after theoperation were similar. Conclusions: The changes in oxygenation can only be explained by an improvementin the lungs ventilation/perfusion ratio. The decelerating inspiratoryflow used in PCV generates higher instantaneous flow peaks andmay allow a better alveolar recruitment. PCV improves oxygenationwithout any side-effects.     

Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency: pathogenesis of impaired acidification

Renal tubular acidosis with osteopetrosis is an autosomal recessive disorder due to deficiency of carbonic anhydrase II (CAII). A 3.5-year-old Egyptian boy with osteopetrosis and cerebral calcification had a persistent normal anion gap type of metabolic acidosis (plasma pH 7.26) and a mild degree of hypokalemia. A baseline urine pH was 7.0; ammonium (NH₄ ⁺) excretion was low at 11 μmol/min per 1.73 m²; fractional excretion of bicarbonate HCO₃ (FE_HCO3) was high at 9%, when plasma HCO₃ was 20 mmol/l; citrate excretion rate was high for the degree of acidosis at 0.35 mmol/mmol creatinine. Intravenous administration of sodium bicarbonate led to a urine pH of 7.6, a FE_HCO3 of 14%, a urine-blood PCO₂ difference of 7 mmHg, NH₄ ⁺ excretion fell to close to nil, and citrate excretion remained at 0.38 mmol/mmol creatinine. Intravenous administration of arginine hydrochloride caused the urine pH to fall to 5.8, the FE_HCO3 to fall to 0, the NH₄ ⁺ excretion rate to rise to 43 μmol/min per 1.73 m², and citrate excretion to fall to <0.01 mmol/mmol creatinine. These results show that our patient had a low rate of NH₄ ⁺ excretion, a low urine minus blood PCO₂ difference in alkaline urine, and a low urinary citrate excretion, but only when he was severely acidotic. He failed to achieve a maximally low urine pH. These findings indicate that his renal acidification mechanisms were impaired in both the proximal and distal tubule, the result of his CA_II deficiency. Received October 24, 1996; received in revised form and accepted February 20, 1997     

Carbon dioxide pneumoperitoneum induces fetal acidosis in a pregnant ewe model

The objective of this study was to evaluate the physiologic consequences of a pneumoperitoneum (pneumo) to the midterm fetus in a pregnant sheep model. The performance of laparoscopic cholecystectomy (LC) during pregnancy is controversial. The primary concern regarding the safety of LC during pregnancy is the physiologic consequences of the CO₂ pneumo to the fetus. Eight ewes with singlet pregnancies between 100 and 120 days of gestation were anesthetized and intubated. Carotid artery and internal jugular catheters were placed in the ewe and in the fetus. Two trocars were placed through the abdominal wall of the ewe and the abdomen was inflated with CO₂ or N₂O at 15 mmHg pressure for 90–120 min. Hemodynamic and blood gas data were obtained every 15 min before, during, and after the pneumo. In two ewes attempts were made to keep maternal Pco₂ constant with hyperventilation. In two other animals the pneumo was increased stepwise in five mmHg increments to 25 mmHg. One fetus succumbed during the CO₂ pneumo, but this animal appeared to be ill during the establishment of invasive monitoring. Fetal respiratory acidosis occurred, reproducibly, after establishment of CO₂ pneumo but did not occur before insufflation or under N₂O pneumo (P<0.0001). Hemodynamic changes were minimal with all agents but it appeared that there a was greater prevalence of fetal tachycardia and hypertension during CO₂ pneumo than during N₂O pneumo. Alterations in ventilator settings based on maternal capnography resulted in late and incomplete correction of respiratory acidosis. Despite clinical reports of successful LC during pregnancy, significant respiratory acidosis may be induced in the fetus with CO₂ pneumo. Alternative gases (e.g., N₂O) or abdominal suspension devices may be preferable to CO₂ when performing laparoscopy in pregnant patients.Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Nashville, TN, 18–19 April 1994     

Muscle surface pH as a monitor of tissue perfusion and acid-base status

Muscle pH, arterial pH, and blood gases were measured in 21 anesthetized dogs. After an initial control period, the animals were subjected to one of the following: major arterial occlusion in the limb being monitored, sever hemorrhage, hypoxia, or hypothermia (28°C). Muscle pH fell rapidly with a decrease in muscle perfusion caused by arterial occlusion or by hemorrhage, without any significant change in arterial pH. In hypoxia, muscle pH varied directly with arterial pH. Hypothermia under anesthesia did not affect muscle pH.     

Die präklinische Blutgasanalyse Teil 1: Der Stellenwert der präklinischen Blutgasanalyse

Prehospital blood gas analysis is a new method in out-of-hospital emergency care. In a prospective pilot study we evaluated the feasibility of prehospital compensation of severe acidosis relying on different monitoring systems to evaluate patients oxygen, carbon dioxide or acid-base status, respectively. Methods: With the help of arterial blood gas checks taken at the site of the emergency, the acid base status of patients undergoing out of hospital cardiopulmonary resuscitation was analysed. The values derived from the first arterial puncture were used to determine the presence and the type of acidosis. The data of the arterial blood gas checks were set into relation with the time elapsed since the beginning of resuscitation and they were compared with end-tidal CO₂. Results: During the observation period 26 blood gas analyses from patients who had out-of-hospital resuscitation because of cardiac arrest were done. Twenty three patients had severe acidosis (pH range <6.9 to 7.31), one had alkalosis (pH 7.51). Only two had an arterial pH within normal range. The pCO₂ was variable (range: 24 to 97 mm Hg). The correlation of pH with time from the beginning of resuscitation to arterial puncture was poor (r=0.407, p<0.05). There was no correlation between pH and BE (r=0.267) or pH and pCO₂, (r=0.016) respectively. Prehospital capnometry had a poor correlation with arterial pCO₂ in most emergeny patients. Only patients with respiratory disturbances of extrapulmonary origin showed a good correlation between end-tidal CO₂ and the arterial pCO₂. In severely ill patients the arterio-alveolar CO₂-difference was unexpectedly high (>15 mm Hg). In four patients resuscitation was not sucessful until compensation of an unexpectedly severe acidosis based upon the findings from blood-gas analysis had been performed. Conclusions: Arterial blood gas analysis proved to be helpful in the optimal management of out of hospital cardiac arrest. The incidence of severe acidosis in patients undergoing cardiopulmonary resuscitation was 80%. The probability of developing acidosis was found to increase slightly depending on the time elapsed since the beginning of CPR. The application of a calculated buffering of acidosis with sodium bicarbonate showed a good outcome in selected cases. In emergency patients alternative methods fail to detect severe disturbances of the patients oxygen and/or carbon dioxide status and the acid-base balance. Management of prehospital cardiac arrest could be optimized by the routine use of blood gas analysis.     

Determination of cardiorespiratory function and the optimum anesthetic regimen during laparoscopic surgery in the rat model

Background: The rat is increasingly being used in laparoscopic research yet the hemodynamic and respiratory effects of CO₂ pneumoperitoneum have not been studied in this model. Methods: Five Lewis rats were anesthetized with inhaled isoflurane (1.4–2.0%) and a 50% O₂/50% N₂O mixture by mask (ISO). Another five rats were anesthetized with 1 ml/kg intraperitoneal sodium pentobarbital (PB) and given 100% O₂ by mask. Catheters were placed in the femoral artery and the right jugular vein and a thermistor probe was placed in the aortic arch. Heart rate (HR), blood pressure (MAP), cardiac index (CI), arterial pH, and PCO₂ were measured at baseline and following 10, 20, and 30 min of 2 mmHg CO₂ pneumoperitoneum. Results: CO₂ pneumoperitoneum had no effect on HR, MAP, CI, pH, or PCO₂ in either the ISO or PB anesthetic groups. Comparing the two anesthetic groups, PB demonstrated a significantly higher MAP at all time points, a significantly higher PCO₂ at baseline, and 10 min of pneumoperitoneum, a significantly lower pH at baseline, 10, and 30 minutes of pneumoperitoneum, and a significantly longer induction time (31 vs. 6 min). There was no difference in HR or CI between the two anesthetics. Conclusion: Low-pressure CO₂ pneumoperitoneum up to 30 min in the spontaneously breathing rat does not significantly affect HR, MAP, CI, pH, or PCO₂. Inhalational isoflurane/N₂O anesthesia produces less hypertension and respiratory acidosis than intraperitoneal pentobarbital during pneumoperitoneum in the rat.     

Extracorporeal CO2 removal and regional citrate anticoagulation in an experimental model of hypercapnic acidosis

Low flow extracorporeal veno‐venous CO₂ removal (ECCO₂R) therapy is used to remove CO₂ while reducing ventilation intensity. However, the use of this technique is limited because efficiency of CO₂ removal and potential beneficial effects on pulmonary hemodynamics are not precisely established. Moreover, this technique requires anticoagulation that may induce severe complications in critically ill patients. Therefore, our study aimed at determining precise efficiency of CO₂ extraction and its effects on right ventricular (RV) afterload, and comparing regional anticoagulation with citrate to systemic heparin anticoagulation during ECCO₂R. This study was performed in an experimental model of severe hypercapnic acidosis performed in two groups of three pigs. In the first group (heparin group), pigs were anticoagulated with a standard protocol of unfractionated heparin while citrate was used for ECCO₂R device anticoagulation in the second group (citrate group). After sedation, analgesia and endotracheal intubation, pigs were connected to a volume‐cycled ventilator. Severe hypercapnic acidosis was obtained by reducing tidal volume by 60%. ECCO₂R was started in both groups when arterial pH was lower than 7.2. Pump Assisted Lung Protection (PALP, Maquet, Rastatt, Germany) system was used to remove CO₂. CO₂ extraction, arterial pH, PaCO₂ as well as systemic and pulmonary hemodynamic were continuously followed. Mean arterial pH was normalized to 7.37 ± 1.4 at an extracorporeal blood flow of 400 mL/min, coming from 7.11 ± 1.3. RV end‐systolic pressure increased by over 30% during acute hypercapnic acidosis and was normalized in parallel with CO₂ removal. CO₂ extraction was not significantly increased in citrate group as compared to heparin group. Mean ionized calcium and MAP were significantly lower in the citrate group than in the heparin group during ECCO₂R (1.03 ± 0.20 vs. 1.33 ± 0.19 and 57 ± 14 vs. 68 ± 15 mm Hg, respectively). ECCO₂R was highly efficient to normalize pH and PaCO₂ and to reduce RV afterload resulting from hypercapnic acidosis. Regional anticoagulation with citrate solution was as effective as standard heparin anticoagulation but did not improve CO₂ removal and lead to more hypocalcemia and hypotension.     

Intracompartmental pressure,P o 2,P co 2and blood flow in the human skeletal muscle

Summary Measurement of P _{O 2},P _{CO 2},and blood flow in skeletal muscle could be a supplement to examination in clinical practice. Mass spectrometry was utilized to measure these parameters in the resting anterior tibial muscle of healthy adults. The partial pressures of oxygen and carbon dioxide were 21 ± 3.6 and 46 ± 2.5 Torr, respectively. The intracompartmental pressure was 8 ± 1.1 Torr. The oxygen tension in muscle varied only slightly when arterial partial pressure was increased. The blood flow (tissue perfusion coefficient) estimated by washout of an inert gas was 5.4 ± 0.8 ml/100 g/min. The results are in accordance with those from animal studies of skeletal muscle. The study demonstrates the feasibility of measuring P _{O 2},P _{CO 2},and blood flow in skeletal muscle by mass spectrometry.     

Oxidative metabolism in experimental Bacteriodies fragilis bactermia

Bacteriodes fragilis has received recent attention as a pathogen in surgical patients. In an effort to assess its pathogenicity, 28 male Sprague-Dawley rats underwent carotid cannulation. With the cannula in the root of the aorta, 14 animals had 1 × 10¹⁰B. fragilis infused over 30 min with a control receiving only saline. This results in an LD₀ despite the number of bacteria being five times the LD₁₀₀ for Escherichia coli. Rats had heart rate, mean arterial pressure, pO₂, pCO₂, pH, hematocrit, glucose, and lactate measured very 2 hr. At 6 hr, the hepatic tissue pO₂ was measured with a surface polyelectrode. Paired experimental and control animals were sacrificed at 6 hr, livers were excised and homogenized. Mitochondria were isolated and studied polarographically by measurement of state 3 (ADP-dependent) and state 4 (ADP-independent) respiratory rates. The Respiratory Control Index (RCI) was calculated (state 3/state 4) as a sensitive indicator of mitochondrial oxygen utilization. No hypotension developed in bacteremic rats. Arterial pO₂, pCO₂, and pH were essentially unchanged. Blood glucose was unchanged while lactate rose moderately. RCIs of experimental and control mitochondria were similar (P > 0.05). B. fragilis bacteremia does not produce the changes of mitochondrial respiratory control of E. coli bacteremia or septic peritonitis.     

Effects of changing hydrogen ion,carbonic acid,and bicarbonate concentrations on bone resorption in vitro

Summary We have examined the effects of H⁺, CO₂, and HCO₃ ⁻ concentrations during metabolic and respiratory acidosis and alkalosis on bone resorption in vitro. Rat fetal bones prelabeled with⁴⁵CaCl₂ were cultured at 2%, 5%, and 10% CO₂ for up to 120 h, and the release of⁴⁵Ca was measured in devitalized bones (non-cell-mediated⁴⁵Ca release) and in live bones (cell-mediated⁴⁵Ca release) cultured with or without PTH and 1,25(OH)₂D₃. Non-cell-mediated mineral loss was linearly related to H⁺ concentration but not to CO₂ or HCO₃ ⁻ concentration. This effect was observed on both labeled and stable calcium. Over a wide pH range (6.9–7.5) H⁺, CO₂, or HCO₃ ⁻ concentrations did not influence cell-mediated bone resorption in control or in PTH-and 1,25(OH)₂D₃-stimulated cultures. However, inhibition of cell-mediated bone resorption was observed at higher or lower pH irrespective of CO₂ or HCO₃ ⁻ concentrations. These observations demonstrate that the bone mineral mobilizing effect of acidosis in vitro is mainly due to the effect of changing H⁺ concentration on devitalized bone. Effects on cell-mediated bone resorption and hormonal response were observed only at extremes of pH. The effects of H⁺ were independent of changes in CO₂ or HCO₃ ⁻ concentration and could be responsible for the negative calcium balance and increased urinary loss observed in metabolic acidosis in vivo, but do not explain the reported differences in effects on calcium metabolism between respiratory and metabolic acidosis.