Point-of-Care Versus Central Laboratory Measurements of Hemoglobin, Hematocrit, Glucose, Bicarbonate and Electrolytes: A Prospective Observational Study in Critically Ill Patients.

INTRODUCTION: Rapid detection of abnormal biological values using point-of-care (POC) testing allows clinicians to promptly initiate therapy; however, there are concerns regarding the reliability of POC measurements. We investigated the agreement between the latest generation blood gas analyzer and central laboratory measurements of electrolytes, bicarbonate, hemoglobin, hematocrit, and glucose. METHODS: 314 paired samples were collected prospectively from 51 critically ill patients. All samples were drawn simultaneously in the morning from an arterial line. BD Vacutainer tubes were analyzed in the central laboratory using Beckman Coulter analyzers (AU 5800 and DxH 800). BD Preset 3 ml heparinized-syringes were analyzed immediately in the ICU using the POC Siemens RAPIDPoint 500 blood gas system. We used CLIA proficiency testing criteria to define acceptable analytical performance and interchangeability. RESULTS: Biases, limits of agreement (±1.96 SD) and coefficients of correlation were respectively: 1.3 (-2.2 to 4.8 mmol/L, r = 0.936) for sodium; 0.2 (-0.2 to 0.6 mmol/L, r = 0.944) for potassium; -0.9 (-3.7 to 2 mmol/L, r = 0.967) for chloride; 0.8 (-1.9 to 3.4 mmol/L, r = 0.968) for bicarbonate; -11 (-30 to 9 mg/dL, r = 0.972) for glucose; -0.8 (-1.4 to -0.2 g/dL, r = 0.985) for hemoglobin; and -1.1 (-2.9 to 0.7%, r = 0.981) for hematocrit. All differences were below CLIA cut-off values, except for hemoglobin. CONCLUSIONS: Compared to central Laboratory analyzers, the POC Siemens RAPIDPoint 500 blood gas system satisfied the CLIA criteria of interchangeability for all tested parameters, except for hemoglobin. These results are warranted for our own procedures and devices. Bearing these restrictions, we recommend clinicians to initiate an appropriate therapy based on POC testing without awaiting a control measurement.

Safety and Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study.

OBJECTIVE: To assess the safety and efficacy of combining extracorporeal CO2 removal with continuous renal replacement therapy in patients presenting with acute respiratory distress syndrome and acute kidney injury. DESIGN: Prospective human observational study. SETTINGS: Patients received volume-controlled mechanical ventilation according to the acute respiratory distress syndrome net protocol. Continuous venovenous hemofiltration therapy was titrated to maintain maximum blood flow and an effluent flow of 45 mL/kg/h with 33% predilution. PATIENTS: Eleven patients presenting with both acute respiratory distress syndrome and acute kidney injury required renal replacement therapy. INTERVENTIONS: A membrane oxygenator (0.65 m) was inserted within the hemofiltration circuit, either upstream (n = 7) or downstream (n = 5) of the hemofilter. Baseline corresponded to tidal volume 6 mL/kg of predicted body weight without extracorporeal CO2 removal. The primary endpoint was 20% reduction in PaCO2 at 20 minutes after extracorporeal CO2 removal initiation. Tidal volume was subsequently reduced to 4 mL/kg for the remaining 72 hours. MEASUREMENTS AND MAIN RESULTS: Twelve combined therapies were conducted in the 11 patients. Age was 70 ± 9 years, Simplified Acute Physiology Score II was 69 ± 13, Sequential Organ Failure Assessment score was 14 ± 4, lung injury score was 3 ± 0.5, and PaO2/FIO2 was 135 ± 41. Adding extracorporeal CO2 removal at tidal volume 6 mL/kg decreased PaCO2 by 21% (95% CI, 17-25%), from 47 ± 11 to 37 ± 8 Torr (p < 0.001). Lowering tidal volume to 4 mL/kg reduced minute ventilation from 7.8 ± 1.5 to 5.2 ± 1.1 L/min and plateau pressure from 25 ± 4 to 21 ± 3 cm H2O and raised PaCO2 from 37 ± 8 to 48 ± 10 Torr (all p < 0.001). On an average of both positions, the oxygenator's blood flow was 410 ± 30 mL/min and the CO2 removal rate was 83 ± 20 mL/min. The oxygenator blood flow (p <0.001) and the CO2 removal rate (p = 0.083) were higher when the membrane oxygenator was placed upstream of the hemofilter. There was no safety concern. CONCLUSIONS: Combining extracorporeal CO2 removal and continuous venovenous hemofiltration in patients with acute respiratory distress syndrome and acute kidney injury is safe and allows efficient blood purification together with enhanced lung protective ventilation.

Interest of a simple on-line screening registry for measuring ICU burden related to an influenza pandemic.

INTRODUCTION: The specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored. An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs. METHODS: We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden. RESULTS: Among the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry. The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non-infected patients for at least three weeks. Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died. The global Flu-OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks. Flu-ORs were significantly higher in University than in non-University hospitals. The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas. CONCLUSIONS: The peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals. An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs.

Right ventricular function during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the effect of mean airway pressure under high-frequency oscillatory ventilation on right ventricular function. DESIGN: Prospective randomized study. SETTING: Intensive care unit of a tertiary care hospital. PATIENTS: Sixteen consecutive patients within the first 48 hrs of mainly pulmonary acute respiratory distress syndrome. INTERVENTIONS: After a 6-hr-period of protective conventional mechanical ventilation, patients were submitted to three 1-hr periods of high-frequency oscillatory ventilation (+5, +10, +15) in a randomized order, with a mean airway pressure level determined by adding 5, 10, or 15 cm H2O to the mean airway pressure recorded during conventional mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Mean airway pressure was 18±3 cm H2O during conventional mechanical ventilation and was increased until 33±3 cm H2O at high-frequency oscillatory ventilation+15. Right ventricular function was assessed using transesophageal echocardiography. During conventional mechanical ventilation, nine patients presented a right ventricular dysfunction (right ventricular end-diastolic area/left ventricular end-diastolic area ratio>0.6) of whom four patients had a right ventricular failure (right ventricular end-diastolic area/left ventricular end-diastolic area ratio>0.9). High-frequency oscillatory ventilation+10 and +15 further worsened right ventricular function, resulting in about a 40% increase in right ventricular end-diastolic area/left ventricular end-diastolic area ratio and a 30% increase in end-diastolic eccentricity index when compared with conventional mechanical ventilation or high-frequency oscillatory ventilation+5 periods. At high-frequency oscillatory ventilation+15, 15 patients had right ventricular dysfunction and nine had right ventricular failure. High-frequency oscillatory ventilation did not improve oxygenation whatever the mean airway pressure level. A significant redistribution of tidal variation to the posterior parts of the lung was observed on electrical impedance tomography measurements when increasing mean airway pressure. However, this redistribution was not observed in patients who presented a worsening of right ventricular function (right ventricular end-diastolic area/left ventricular end-diastolic area increase>40%) at high-frequency oscillatory ventilation+15. CONCLUSIONS: In patients with mainly pulmonary acute respiratory distress syndrome, using high mean airway pressure under high-frequency oscillatory ventilation can worsen right ventricular function when compared with protective conventional mechanical ventilation, notably in patients in whom high-frequency oscillatory ventilation produced less alveolar recruitment of the posterior parts of the lungs. This study highlights the interest of monitoring right ventricular function during high-frequency oscillatory ventilation.

One collective case of type A foodborne botulism in Corsica.

Foodborne botulism is rare in 21st century Western Europe. The purpose of this report is to describe a collective case of type A botulism caused by ingestion of artisanal-produced food (canned green beans and/or salted roast pork). Five of the seven persons who shared the meal presented signs of severe intoxication leading to the fatal respiratory failure in one 18-year-old girl. Three patients required mechanical ventilation for durations ranging from 37 to 78 days and developed severe infectious, respiratory and/or psychiatric complications. In 4 out of the 5 patients, trivalent antitoxin was administered between days 2 and 7 but did not avoid the need for long-term intubation/mechanical ventilation. Treatment with 3,4-diaminopyridine was ineffective in the 26-year-old man who required long-term breathing assistance. This case of collective foodborne botulism illustrates the potential severity of this hazard.

Effect of fluid loading during hypovolaemic shock on caspofungin pharmacokinetic parameters in pig.

INTRODUCTION: Caspofungin treatment is frequently initiated in shock patients. In the present study, we investigated the influence of hypovolaemic shock requiring fluid loading on the plasma and pulmonary pharmacokinetic parameters of caspofungin in the pig. METHODS: After being anaesthetised and mechanically ventilated, 12 pigs were bled to induce a two-hour deep shock and resuscitated using normal saline based on haemodynamic goals. A one-hour infusion of 70 mg of caspofungin was started at the beginning of the resuscitation period. The lungs were removed four hours after caspofungin administration. Sixteen animals served as controls without haemorrhage. Caspofungin concentrations were measured by using high-performance liquid chromatography, and a two-compartment population pharmacokinetic analysis was performed. RESULTS: In the shock group, the volume of blood removed was 39 ± 7 mL/kg and a volume of 90 ± 17 mL/kg saline was infused throughout the resuscitation period. The extravascular lung water index was higher in the shock group (9.3 ± 1.6 mL/kg vs 5.7 ± 1 mL/kg in the control group; P < 0.01). In the shock group, the median (interquartile range) maximal plasma concentration was 37% lower than in the control group (21.6 µg/mL (20.7 to 22.3) vs 33.1 µg/mL (28.1 to 38.3); P < 0.01). The median area under curve (AUC) from zero to four hours was 25% lower in the shock group than in the control group (60.3 hours × µg/mL (58.4 to 66.4) vs 80.8 hours × µg/mL (78.3 to 96.9); P < 0.01), as was the median lung caspofungin concentration (1.22 µg/g (0.89 to 1.46) vs 1.64 µg/g (1.22 to 2.01); P < 0.01). However, the plasma-to-tissue ratios were not different between the groups, indicating that lung diffusion of caspofungin was not affected after shock followed by fluid loading. Pharmacokinetic analysis showed that the peripheral volume of distribution of caspofungin and intercompartmental clearance were significantly higher in the shock group, as was the total apparent volume of distribution. CONCLUSIONS: Hypovolaemic shock followed by fluid loading in the pig results in a significant increase in the apparent volume of distribution of caspofungin and in a decrease in its plasma and pulmonary exposition. Although our model was associated with capillary leakage and pulmonary oedema, our results should be generalised to the septic shock with caution. Future investigations should focus on monitoring plasma caspofungin concentrations and optimal caspofungin dosing in shock patients.

Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study.

PURPOSE: To compare characteristics, clinical evolution and outcome in adult patients with influenza A (H1N1) acute respiratory distress syndrome (ARDS) treated with or without extracorporeal membrane oxygenation (ECMO). METHODS: A prospective observational study of patients treated in Marseille South Hospital from October 2009 to January 2010 for confirmed influenza A (H1N1)-related ARDS. Clinical features, pulmonary dysfunction and mortality were compared between patients treated with and without ECMO. RESULTS: Of 18 patients admitted, 6 were treated with veno-venous and 3 with veno-arterial ECMO after median (interquartile, IQR) duration of mechanical ventilation of 10 (6-96) h. Six ECMO were initiated in a referral hospital by a mobile team, a median (IQR) of 3 (2-4) h after phone contact. Before ECMO, patients had severe respiratory failure with median (IQR) PaO2 to FiO2 ratio of 52 (50-60) mmHg and PaCO2 of 85 (69-91) mmHg. Patients treated with or without ECMO had the same hospital mortality rate (56%, 5/9). Duration of ECMO therapy was 9 (4-14) days in survivors and 5 (2-25) days in non-survivors. Early improvement of PaO(2) to FiO2 ratio was greater in ECMO survivors than non-survivors after ECMO initiation [295 (151-439) versus 131 (106-144) mmHg, p < 0.05]. Haemorrhagic complications occurred in four patients under ECMO, but none required surgical treatment. CONCLUSIONS: ECMO may be an effective salvage treatment for patients with influenza A (H1N1)-related ARDS presenting rapid refractory respiratory failure, particularly when provided by a mobile team allowing early cannulation prior to transfer to a reference centre.

FIO2 and acute respiratory distress syndrome definition during lung protective ventilation.

OBJECTIVE: PaO2/FIO2 ratio (P/F) is the marker of hypoxemia used in the American-European Consensus Conference on lung injury. A high FIO2 level has been reported to variably alter PaO2/FIO2. We investigated the effect of high FIO2 levels on the course of P/F in lung protective mechanically ventilated patients with acute respiratory distress syndrome. DESIGN: Prospective, controlled, interventional study. SETTING: University teaching French medical intensive care unit. PATIENTS: Twenty-four patients with acute respiratory distress syndrome having P/F between 100 and 200 mm Hg at FIO2 0.5 received low-volume controlled ventilation (V(T) = 6 mL/kg predicted body weight) with a positive end-expiratory pressure at 2 cm H2O above the lower inflection point if present, or 10 cm H2O. INTERVENTION: The following FIO2 levels were applied randomly for 20 mins: 0.5, 0.6, 0.7, 0.8, 0.9, and 1. MEASUREMENTS AND RESULTS: Increasing FIO2 above 0.7 was associated with a significant increase in P/F (p < 0.001). The mean P/F change between FIO2 0.5 and 1 (Delta P/F) was 47% +/- 35%. Sixteen patients (67%) had a P/F >200 at FIO2 1 whereas P/F was <200 at FIO2 0.5. Venous admixture (Q(VA)/Q(T)) decreased linearly for each FIO2 step (p < 0.001). The Q(VA)/Q(T) change between FIO2 0.5 and 1 was strongly correlated with Delta P/F (r = 0.84). Delta P/F was higher in patients with true shunt <30% (64% [54-93]) than in those with shunt >30% (20% [10-36]; p = 0.003). CONCLUSION: The P/F ratio increased significantly with a FIO2 >0.7. P/F variation, induced by a switch from FIO2 0.5 to 1, was responsible for two thirds of patients changing from the acute respiratory distress syndrome to the acute lung injury stage of the American-European Consensus Conference definition. FIO2 should be carefully defined for the screening of lung-injured patients.

Effect of hypertonic saline pre-treatment on ischemia-reperfusion lung injury in pig.

BACKGROUND: Hypertonic saline may be administered in the setting of lung transplantation but may affect the development of ischemia-reperfusion lung injury. This study investigated the effects of the pre-treatment by intravenous hypertonic saline in a pig model of single lung ischemia-reperfusion. METHODS: Forty-three pigs (34 +/- 4 kg) under mechanical ventilation were randomly assigned to a left lung ischemia-reperfusion alone or preceded by 4-ml/kg 7.5% hypertonic saline, 33-ml/kg normal saline, or by the infusion of the vasodilator nicardipine. Animals without ischemia served as controls. After euthanasia, the left lung was sampled for histologic analysis and measurement of lung water and alveolar-capillary permeability. RESULTS: Ischemia-reperfusion resulted in high-permeability pulmonary edema, hypoxemia, and increased interleukin-6 serum level. Hypertonic saline pre-treatment worsened pulmonary edema of the left lung (6.6 +/- 0.7 vs 4.8 +/- 0.8 ml/kg of body weight, p < 0.05) and resulted in a higher ratio of the protein level in the alveolar fluid to the serum protein level (0.41 +/- 0.04 vs 0.21 +/- 0.09, p < 0.05) and in a higher histologic damage score (11 [range, 9-11.75] vs 6.5 [range, 4.5-7.5], p < 0.05) without promoting pulmonary or systemic inflammation. Lung injury was affected neither by normal saline nor by nicardipine pre-treatment. Nicardipine did not influence the deleterious effect of hypertonic saline. CONCLUSIONS: Pre-treatment by intravenous hypertonic saline worsened ischemia-reperfusion lung injury independently of its effects on the cardiac index or pulmonary circulation but probably through a direct effect of hyperosmolarity on endothelial permeability.