Is the lactate value predictive of the return of spontaneous circulation during CPR in nontraumatic OHCA?

AIM OF THE STUDY: Cardiac arrest is a major public health issue, in which emergency medical services (EMS) initiating or continuing resuscitation in about 50% to 60% of cases. The aim of this study was to determine whether blood lactate levels and their course during cardiopulmonary resuscitation are prognostic indicators of the return of spontaneous cardiac activity (ROSC) in non-traumatic out-of-hospital cardiac arrest (OHCA). METHODS: This was a prospective, interventional, multi-center study between 2017 and 2020. Patients above the age of 18 years (>50 years for women) who had non-traumatic OHCA and did not achieve ROSC before the arrival of the EMS, and for whom the medical team decided to initiate or continue cardiopulmonary resuscitation have been included. The primary endpoint was the return of spontaneous cardiac activity during out-of-hospital cardiopulmonary resuscitation, and secondary endpoint was survival at day 28. The lactate was initially measured simultaneously on a venous and capillary sample and then in capillary samples throughout the CPR, using POC device. RESULTS: A total 60 patients were included. Median age was 71 [IQR: 62-84] and 21.3% were female. Among them, 25% underwent ROSC in out-of-hospital setting, and 13,3% were alive at D-28. The median venous lactate value in all patients at T0 (time at which the EMS set up the peripheral venous line) was 6.2 mmol/L [IQR: 4.6-8.1], with no difference between patients with or without ROSC: 6.4 mmol/L [IQR:4.7-7.9] for patients with ROSC and 6.2 mmol/L [IQR: 4.7-8] for patients without ROSC (p = 0.87). The variables independently associated with ROSC were initial EtCo2 value (aOR = 1.12; 95% CI 1.01-1.25); the initial shockable rhythm (aOR = 10.2; 95% CI 1.18-88.2); and the pre-ROSC adrenaline dose (aOR = 0.54; 95% CI 0.35-0.82). CONCLUSION: In this prospective multi-center study, there was no independent association between lactate values during cardiopulmonary resuscitation and ROSC in non-traumatic OHCA. However, the post-ROSC pre-hospital kinetics of lactate (i.e., during the first 30 min) seem to be associated with survival.

[Assessment of a post-emergency pathway with early urological regulation]. / Analyse d'un modèle de circuit court post-urgence avec une régulation précoce urologique.

INTRODUCTION: Urological emergencies represent 7 % of the outpatients at the emergency department (ED). We assessed the effect of setting up a post-emergency consultation (CPU) after deferred urological medical regulation. METHODS: All patients admitted to the ED in a university center over the period December 2017 to July 2018 and for whom a CPU was scheduled were included. The regulation concerned the date of CPU and supplementary exams. The main outcome was the ability to provide an efficient response according to a predefined grid of specific solutions. RESULTS: One hundred and twenty-eight patients were included. The median age was 57 years (18-97). Efficacy of the CPU was 76 %. This rate was lower in no-show patients or consulting for rare and complex motives (47 %, n=60). The no-show were not reachable on the first call in 51.6 % of cases, with a similar age and motives distribution to the others. Only 6,9 % (n=128) of all consultants (n=1863) had been referred to the CPU by emergency physicians. The decision was a second consultation in 70 % (48), a new exam in 10 % (7), deferred emergency surgery in 12 % (8) and finally 18 % (12) of no follow-up. CONCLUSION: CPU following early regulation by a urologist provides an effective response in 76 % of situations. Assessment of "no-shows" helped to identify groups at risk. LEVEL OF EVIDENCE: III.

The place of simulation in the surgical resident curriculum. The pedagogic program of the Nice Medical School Simulation Center.

INTRODUCTION: Surgical training relies on medical school lectures, practical training in patient care and in the operating room including instruction in anatomy and experimental surgery. Training with different techniques of simulators can complete this. Simulator-based training, widely used in North America, can be applied to several aspects of surgical training without any risk for patients: technical skills in both open and laparoscopic surgery, the notion of teamwork and the multidisciplinary management of acute medicosurgical situations. METHOD: We present the curriculum developed in the Simulation Center of the Medical School of Nice Sophia-Antipolis. All residents in training at the Medical School participate in this curriculum. RESULTS: Each medical student is required to pursue theoretical training (familiarization with the operating room check-list), training in patient management using a high fidelity mannequin for various medical and surgical scenarios and training in technical gestures in open and laparoscopic surgery over a 2-year period, followed by an examination to validate all technical aptitudes. This curriculum has been approved and accredited by the prestigious American College of Surgeons, making this the first of its kind in France. CONCLUSION: As such, it should be considered as a model and, in accordance to the wishes of the French Surgical Academy, the first step toward the creation of true schools of surgery.

[Secondary hyperkalaemic acute flaccid tetraplegia]. / Tétraplégie flasque aiguë secondaire à une hyperkaliémie.

A 57-year-old man with chronic renal failure and multiple vascular diseases presented an acute flaccid tetraplegia. Blood tests revealed renal failure with serum potassium of 9.69 mmol/l. The medullar and brain MRI were normal. The correction of the hyperkalaemia led to a fast and complete neurological recovery. This fact confirmed the diagnosis of secondary hyperkalaemic tetraplegia.

Sevoflurane but not propofol increases interstitial glycolysis metabolites availability during tourniquet-induced ischaemia-reperfusion.

BACKGROUND: Ischaemia/reperfusion (I/R) is one of the main pathophysiological phenomena involved in the anaesthetic practice. The authors hypothesized that anaesthetic regimens can influence skeletal muscle tolerance to tourniquet-induced I/R that should be reflected by the interstitial metabolite levels of anaerobic glycolysis. METHODS: Microdialysis probes were implanted in three groups of 10 patients each receiving either sevoflurane (SEVO), propofol (PRO), or spinal (SA) anaesthesia (for induction and maintenance). SA group was considered as a control group. Interstitial fluid was obtained during tourniquet-induced I/R and was analysed for interstitial glucose, lactate, pyruvate, and glycerol. RESULTS: The microdialysis flow rate was 0.5 microl min(-1). Compared with the control group, the SEVO group had a higher level of both lactate and pyruvate and an increase in glucose during ischaemia. In contrast, the PRO group had a lower level of pyruvate, resulting in a significant higher increase (eight times from baseline) of the lactate pyruvate ratio. Glucose level remained low in this group. During reperfusion, lactate, pyruvate, and glucose remained at a significantly higher level in the SEVO group. In the PRO group, there was no difference in lactate, pyruvate, and glucose levels compared with the control group. The interstitial level of glycerol exhibits only few and comparable changes during I/R between the groups. CONCLUSIONS: Our results indicate that there is a better availability of interstitial glycolysis metabolites (glucose, lactate, and pyruvate) in the skeletal muscle during ischaemia and reperfusion after sevoflurane exposure than after propofol, suggesting a potential preconditioning effect of sevoflurane on tourniquet-induced skeletal muscle I/R.

[Kyphoscoliosis and ascending aortic aneurysm: a new case of intermittent right-to-left shunting through a patent foramen oval]. / Anévrisme de l'aorte ascendante et cyphoscoliose: un nouveau cas de shunt droit-gauche intermittent par un foramen ovale perméable.

Platypnaea-orthodeoxia syndrome is usually due to an atrial right-to-left shunt through a patent foramen ovale. We report a case of foramen ovale reopened an unusual circumstance. A 83-year-old patient presenting back pains since a few days was admitted in emergency for dyspnaea and refractory hypoxia. The only way to control her back pains was to stay seated in a kyphoscoliosis position. The imagery explorations pointed out an ascending aortic aneurysm, which compressed the right atrium and distorted the position of the atrial septum relative to caval inflow, when the patient was in her painless position, explaining this gravity-related refractory hypoxia.

Effects of acetylcysteine and ischaemic preconditioning on muscular function and postoperative pain after orthopaedic surgery using a pneumatic tourniquet.

BACKGROUND AND OBJECTIVE: The use of a pneumatic tourniquet can induce muscular and neurological complications in the operated limb. The genesis of these injuries could involve an ischaemia/reperfusion phenomenon and a compression under the cuff. We evaluated effects of an antioxidant, acetylcysteine and ischaemic preconditioning on the rhabdomyolysis and postoperative pain following a knee ligamentoplasty using a pneumatic tourniquet. METHODS: We included 31 patients scheduled for a knee ligamentoplasty randomly assigned in three groups (control, acetylcysteine 1200 mg the day before and 600 mg at the operative day, ischaemic preconditioning). RESULTS: There was a moderate rise in myoglobin and creatinine phosphokinase with no significant difference between the three groups. The muscular functional parameters were similar in all the groups. However, the morphine consumption within the first 48 h was smaller in the treatment groups (0.22 +/- 0.31 mg kg-1 and 0.22 +/- 0.23 mg kg-1 in the preconditioning and antioxidant groups, respectively) than in the control group (0.47 +/- 0.33 mg kg-1, P <0.05). CONCLUSIONS: Acetylcysteine and ischaemic preconditioning do not decrease the extent of rhabdomyolysis related to the use of a pneumatic tourniquet and do not improve the postoperative muscle recovery. On the other hand, they allow a significant reduction in the postoperative morphine consumption.

[Metformin-associated lactic acidosis remains a serious complication of metformin therapy]. / L'acidose lactique reste une complication grave du traitement par metformine.

We report 4 cases of lactic acidosis in diabetic patients usually treated with metformin. For the first 3 patients, the clinical history was similar because lactic acidosis was precipitated by gastro-intestinal disorders whereas all of them were simultaneously treated with several nephrotoxic drugs. These 3 patients presented with acute renal failure on arrival at hospital. Their issue was fatal whereas any obvious cause of overproduction of lactate was found. The fourth case, which was due to a voluntary intoxication, was the only one presenting with a favourable evolution. The metformin plasma and red blood cell levels were performed for 2 of 4 patients and confirmed the overdose. These observations remind that metformin-associated lactic acidosis remains a serious complication, and that medical doctors must respect strictly contra-indications and guidelines for withdrawing metformin.

[Rapid sequence intubation in emergency: is there any place for fentanyl?]. / Induction à séquence rapide en urgence: quelle est la place du fentanyl?

OBJECTIVES: Rapid sequence intubation (RSI) with the association of etomidate and succinylcholine is the French "Gold standard" for urgent "full stomach" endotracheal intubations. The aim of this study is to assess the fentanyl as a co-induction agent to take over the sedation between the RSI and the keeping of sedation, which is a critical period in which harmful neuro-vegetatives events, and awakening signs are frequently seen. STUDY DESIGN: Randomized, double blind controlled prospective study, after acceptation by the local ethical committee. PATIENTS AND METHODS: Three groups of patients undergoing RSI in the intensive care unit and by the out-of-hospital medical team were compared: group A patients received fentanyl 3 micrograms kg-1 during RSI, before paralysis was induced. Group B patients received the same dose of fentanyl immediately after endotracheal intubation. Group C patients did not received fentanyl (control group). Outcome measures were awakening signs arrival (respiratory movements, eyes opening, spontaneous limb movements), Ramsay score assessment, and haemody namics. Attempt at intubation and vomiting incident were also measured. Discrete data were compared by chi-2 analysis, continuous data were compared with two-way analysis of variance. A p value < 0.05 was the significant threshold. RESULTS: Thirty-six patients were enrolled and completed the study. All the included patients presented awakening signs. The use of fentanyl did not prevent the recourse of other sedative medications. Ten minutes after endotracheal intubation, significant differences has been noticed for the awakening signs arrival between fentanyl groups (A: 42% and B: 36%) and control group (C: 77%). The Ramsay score evolution follows the same variation. All the patients were intubated on the first attempt, there was no vomiting incident noticed. CONCLUSION: The use of fentanyl, as a co-induction agent with etomidate and succinylcholine during RSI, allows a significant delay of the awakening signs arrival and attenuate the neurovegetative response during the minutes after endotracheal intubation after RSI, without deleterious haemodynamic effects.

Acute postoperative metabolic complications of diabetes.

Because of several factors, including a change in the hormonal behavior, the postoperative period is at high risk for the diabetic patient to present a metabolic complication. On the other hand, a diabetic metabolic disorder may be secondary and reveal a severe underlying complication (sepsis...). Ketoacidosis is the consequence of an absolute or relative lack of insulin and occurs mainly in insulin dependent diabetic patients. Its incidence should be very low during the postoperative period since insulin protocols are systematically used. The main clinical and biological signs are a polypnea, signs of dehydration, an hyperglycemia associated with a high anion gap metabolic acidosis and the presence of ketoacids in the urine. Its treatment is mainly based on an active rehydration and an insulin and potassium supply. Sodium bicarbonate should not be used systematically any more, even during severe acidosis. Hyperosmolar non ketotic states affects insulin nondependent and older diabetic patients for the most part and occurs under similar conditions than ketoacidosis, revealing most of the time a severe underlying complication. Clinical and biological manifestations include a severe dehydration, alterations in consciousness and a major hyperglycemia associated to a moderate or mild metabolic acidosis. Its main treatment is an active rehydration and insulin plus potassium in a second time. Hypoglycemia is usually the consequence of a mistake in the diabetes care and in the insulin management. Every sickness or consciousness disorder occurring in a diabetic patient treated with insulin should lead to perform a blood glucose measurement. In case of severe manifestations, glucose should be administered in emergency, orally if the patient is conscious or intravenously if he is not. Lactic acidosis occurring during the postoperative period in a diabetic patient is usually non specific of diabetic disease and reflects the existence of an underlying complication (sepsis, hemorrhage, hypoxia,...), as it would in an non diabetic patient. Lactic acidosis due to a treatment with metformin is now very rare and occurs almost only in patients having a contraindication to the use of metformin.

Initial effect of sodium bicarbonate on intracellular pH depends on the extracellular nonbicarbonate buffering capacity.

OBJECTIVE: The effect of sodium bicarbonate on intracellular pH under conditions close to those in vivo, with both bicarbonate and nonbicarbonate buffering systems, is unknown. We postulated that this effect depends on the nonbicarbonate buffering capacity because the alkali-induced back-titration of these buffers results in a concentration-dependent release of CO2 in the extracellular space, leading to a decrease in intracellular pH. DESIGN: The study was conducted in two stages. First, human hepatocytes were perfused with pH 7 bicarbonate-buffered medium (5 mM HCO3-, 20 torr Pco2) containing no nonbicarbonate buffer or small amounts (5 mM 4-[2-hydroxyethyl]-1-piperazineethanesulfonic acid [HEPES]) or large amounts (20 mM HEPES) of nonbicarbonate buffer. Second, the changes in intracellular pH of hepatocytes placed in acidotic human blood (pH 7, 5 mM HCO3-, 20 torr Pco2) at three hematocrits (40%, 20%, and 5%) were measured. SETTING: Research laboratory at a medical university. SUBJECTS: Cryopreserved human hepatocytes thawed the day before the experiments. INTERVENTIONS: Sodium bicarbonate was infused for 10 mins to increase the HCO3- concentration from 5 to 30 mM. In the second part, 20 mM sodium bicarbonate was added directly to the blood bathing the cells. MEASUREMENTS AND MAIN RESULTS: The intracellular pH was measured with the pH-sensitive fluorescent dye bis-carboxyethyl carboxy-fluorescein in its esterified form, acetoxy-methyl ester, by using a single-cell imaging technique. Gas analyses were performed before and during the sodium bicarbonate load. Sodium bicarbonate caused a decrease in intracellular pH with all media except the artificial medium containing no HEPES. This decrease was small in media with low nonbicarbonate buffering capacity (5 mM HEPES and 5% hematocrit blood) and large in media with high nonbicarbonate buffering capacity (20 mM HEPES and 40% hematocrit blood). The change in intracellular pH was linked closely to the change in Pco2 caused by the sodium bicarbonate. CONCLUSIONS: The effect of sodium bicarbonate on intracellular pH depends on changes in Pco2 in the medium bathing the cells. The increase in Pco2 is correlated with the extracellular nonbicarbonate buffering capacity because of the release of H+ ions coming from the back-titration of these buffers. We conclude that sodium bicarbonate may exacerbate cell acidosis under buffering conditions close to those in vivo and that the initial changes in cell pH caused by sodium bicarbonate depend on the extracellular nonbicarbonate buffering capacity.

The increase in CO2 production induced by NaHCO3 depends on blood albumin and hemoglobin concentrations.

OBJECTIVE: To evaluate the origin of H+ ions participating in the generation of CO2 coming from sodium bicarbonate infusion during metabolic acidosis. We hypothesized that these H+ ions come from a back-titration of the main non-bicarbonate buffers present in the blood, i. e. the hemoglobin and the albumin, and thus postulated that the rate of CO2 release from a bicarbonate load is dependent on the concentration of these buffers. DESIGN: Prospective clinical and experimental study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS AND MATERIAL: (1) Sixteen stable sedated and artificially ventilated critically ill patients with a mild base deficit. (2) Acidotic human blood (bicarbonate 5 mM, pH 7.0) of hematocrit 5, 10, 20 and 40% regenerated from a mixture of frozen fresh plasma and packed red blood cells. PATIENTS: infusion of 1.5 mmol/kg sodium bicarbonate over 5 min. Regenerated blood: 25 mM sodium bicarbonate load. PATIENTS: continuous measurement of CO2 production (VCO2) on the expired gas using a metabolic monitor and arterial blood gas analysis before (T0), at the end (T5) and at 10, 30 and 60 min after the beginning of the bicarbonate infusion. The increase in VCO2 was 18 +/- 7% leading to a rise in PaCO2 from 39.6 +/- 2.3 at T0 to 46.2 +/- 2.7 mmHg at T5. The increases in VCO2 and in PaCO2 were significantly correlated to the albumin (r = 0.73, p < 0.005 and r = 0.70, p < 0.005, respectively) and to the hemoglobin (r = 0.51, p < 0.05 and r = 0.65, p < 0.01, respectively) concentrations. Regenerated blood: gas analysis 1 min after the bicarbonate load. The increase in PCO2 was closely related to the hematocrit (Ht) of the blood as it was 15.9 +/- 7.5 mmHg for Ht 5%, 29.0 +/- 9.6 for Ht 10%, 44.2 +/- 5.9 for Ht 20% and 71.0 +/- 3.5 for Ht 40% (n = 5 for each, p < 0.001). CONCLUSIONS: The importance of the release of CO2 from a bicarbonate load is dependent on the concentration of the blood non-bicarbonate buffers. It is therefore likely that the adverse effects of bicarbonate therapy linked to the CO2 generation are more important in patients with high blood albumin and hemoglobin concentrations.

Hypocapnia does not alter hepatic blood flow or oxygen consumption in patients with head injury.

OBJECTIVE: To evaluate the effects of hypocapnia on the systemic and hepatic circulations and oxygenation values in patients with head injury. DESIGN: Open-label, prospective study. SETTING: University hospital, department of anesthesiology and intensive care unit. PATIENTS: Eleven mechanically ventilated patients with isolated head trauma and stable hemodynamic status. INTERVENTIONS: At the beginning of the study, each patient presented with normocapnic ventilation. Mechanical hyperventilation was then adjusted to obtain stable hypocapnia over an interval of 24 hrs. Cardiac output and other systemic hemodynamic parameters were measured, using a pulmonary artery catheter. Hepatic parameters were measured via a catheter inserted into the hepatic vein. Total hepatic blood flow was determined by the Fick principle using a continuous infusion of indocyanine green. Arterial and hepatic venous blood gases were sampled to determine systemic and hepatic-splanchnic oxygenation. Measurements were done at the end of the four phases: a) 30 mins of normocapnia (N); b) 30 mins of hypocapnia (H0); c) 3 hrs of hypocapnia (H3); and d) 24 hrs of hypocapnia (H24). Intracranial pressure and cerebral perfusion pressure were hourly monitored throughout the study. MEASUREMENTS AND MAIN RESULTS: There were no significant changes in systemic hemodynamic parameters. The hepatic blood flow index did not differ from normocapnia (N 1.8 +/- 0.4 L/min/m2) to hypocapnia (H0 1.6 +/- 0.3 L/min/m2; H3 1.7 +/- 0.4 L/min/m2; H24 1.7 +/- 0.4 L/min/m2). The ratio of hepatic blood flow index to cardiac index remained stable throughout the study. Hypocapnia did not affect hepatic-splanchnic oxygen delivery and consumption. CONCLUSIONS: Hypocapnic hyperventilation does not alter hepatic hemodynamic parameters in patients with head injury. This result may be related to the lack of changes in cardiac output or in the hepatic vasoreactivity. Moreover, hypocapnia does not modify hepatic-splanchnic oxygenation. Thus, in case of intracranial hypertension, hypocapnia might be used without undesirable effect on the hepatic-splanchnic perfusion.

Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction.

A prospective study was conducted on 34 stable septic patients to determine whether mild hyperlactatemia is a marker of lactate overproduction or an indicator of lactate underutilization during sepsis. Plasma lactate clearance and lactate production were evaluated by modeling the lactate kinetic induced by an infusion of 1 mmol/kg L-lactate over 15 min. The patients were divided in two groups depending on their blood lactate: < or = 1.5 mmol/L (n = 20, lactate = 1.2+/-0.2 mmol/L) or > or = 2 mmol/L (n = 10, lactate = 2.6+/-0.6 mmol/L). The hyperlactatemic patients had a lower lactate clearance (473+/-102 ml/kg/h) than those with normal blood lactate (1,002+/-284 ml/kg/h, p < 0.001), whereas lactate production in the two groups was similar (1,194+/-230 and 1,181+/-325 micromol/kg/h, p = 0.90). A second analysis including all the patients confirmed that the blood lactate concentration was closely linked to the reciprocal of lactate clearance (r2 = 0.73, p < 0.001) but not to lactate production (r2 = 0.03, p = 0.29). We conclude that a mild hyperlactatemia occurring in a stable septic patient is mainly due to a defect in lactate utilization.

Reliability of anion gap as an indicator of blood lactate in critically ill patients.

OBJECTIVE: To evaluate the sensitivity, specificity, and predictive values of an elevated anion gap as an indicator of hyperlactatemia and to assess the contribution of blood lactate to the serum anion gap in critically ill patients. DESIGN: Prospective study. SETTING: General intensive care unit of a university hospital. PATIENTS: 498 patients, none with ketonuria, severe renal failure or aspirin, glycol, or methanol intoxication. MEASUREMENTS AND RESULTS: The anion gap was calculated as [Na+]-[Cl-]-[TCO2]. Hyperlactatemia was defined as a blood lactate concentration above 2.5 mmol/l. The mean blood lactate concentration was 3.7 +/- 3.2 mmol/l and the mean serum anion gap was 14.3 +/- 4.2 mEq/l. The sensitivity of an elevated anion gap to reveal hyperlactatemia was only 44% [95% confidence interval (CI) 38 to 50], whereas specificity was 91% (CI 87 to 94 and the positive predictive value was 86% (CI 79 to 90). As expected, the poor sensitivity of the anion gap increased with the lactate threshold value, whereas the specificity decreased [for a blood lactate cut-off of 5 mmol/l: sensitivity = 67% (CI 58 to 75) and specificity = 83% (CI 79 to 87)]. The correlation between the serum anion gap and blood lactate was broad (r2 = 0.41, p < 0.001) and the slope of this relationship (0.48 +/- 0.026) was less than 1 (p < 0.001). The serum chloride concentration in patients with a normal anion gap (99.1 +/- 6.9 mmol/l) was comparable to that in patients with an elevated anion gap (98.8 +/- 7.1 mmol/l). CONCLUSIONS: An elevated anion gap is not a sensitive indicator of moderate hyperlactatemia, but it is quite specific, provided the other main causes of the elevated anion gap have been eliminated. Changes in blood lactate only account for about half of the changes in anion gap, and serum chloride does not seem to be an important factor in the determination of the serum anion gap.

Effect of continuous venovenous hemofiltration with dialysis on lactate clearance in critically ill patients.

OBJECTIVE: To evaluate the effect of continuous venovenous hemofiltration with dialysis on lactate elimination by critically ill patients. DESIGN: Prospective, clinical study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Ten critically ill patients with acute renal failure and stable blood lactate concentrations. INTERVENTIONS: Two-stage investigation: a) measurement of lactate concentrations in samples of serum and ultradiafiltrate from patients receiving continuous venovenous hemofiltration with dialysis to calculate lactate clearance by the hemofilter; b) evaluation of total plasma lactate clearance by infusing sodium L-lactate (1 mmol/kg of body weight) over 15 mins. MEASUREMENTS AND MAIN RESULTS: Arterial lactate concentration was determined before, during, and after the infusion. Lactate elimination variables were calculated from the plasma curve using model-independent and model-dependent estimates (by software). At the end of the infusion, median blood lactate concentration increased from 1.4 mmol/L (range 0.8 to 2.6) to 4.8 mmol/L (range 2.4 to 5.7) and returned to 1.6 mmol/L (range 0.9 to 3.4) 60 mins later. The median total plasma lactate clearance was 1379 mL/min (range 753.7 to 1880.7) and the median filter lactate clearance was 24.2 mL/min (range 7.1 to 35.6). Thus, filter lactate clearance accounted for < 3% of total lactate clearance. CONCLUSIONS: Continuous venovenous hemofiltration with dialysis cannot mask lactate overproduction, and its blood concentration remains a reliable marker of tissue oxygenation in patients receiving this renal replacement technique.

Effect of sodium bicarbonate on intracellular pH under different buffering conditions.

Previous in vitro studies have reported a paradoxical exacerbation of intracellular acidosis following bicarbonate therapy due to the generated CO2 entering the cytoplasm. However, these studies were conducted in nonphysiological Hepes-buffered media. We compared the effect of a sodium bicarbonate load on the intracellular pH (pHi) of hepatocytes placed in nonbicarbonate (NBBS) or bicarbonate (BBS) buffering systems. The pHi of isolated rat hepatocytes was measured using the fluorescent pH sensitive dye BCECF and a single-cell imaging technique. Cells were placed in medium buffered with HCO3-/CO2 or Hepes. All media were adjusted to pH 7 with L-lactic acid or HCl. An acute 45 mM sodium bicarbonate load was added to each medium and the changes in pHi were measured every three seconds for 90 seconds. The sodium bicarbonate load caused rapid cytoplasmic acidification of cells in NBBS (N = 50, P < 0.001). In contrast, hepatocytes in BBS underwent a marked increase in pHi (N = 50, P < 0.001) without any initial decrease in pHi. These differences were highly significant for the buffer (P < 0.01), but not for the acid used. We conclude that sodium bicarbonate exacerbates intracellular acidosis only in a NBBS. Hence, in vitro studies reporting a paradoxical intracellular acidosis following bicarbonate therapy cannot be extrapolated to the in vivo buffering conditions, and should not be used to argue against bicarbonate therapy.