Lessons learnt from quality improvement collaboratives in Cambodia.

Currently, Cambodia uses performance-based financing (PBF) and a national quality enhancement monitoring system as key components of its strategy to achieve universal health coverage and the health-related Sustainable Development Goals. PBF is one among many strategies to improve the quality of healthcare services and its effects and limitations have been widely documented. We share lessons learnt from the use of quality improvement collaboratives, a facility-based quality improvement strategy, to amplify and complement PBF to address specific service delivery gaps, improve provider competency, and increase patient trust and satisfaction in the health system, a driver of healthcare utilisation.

Impact of levosimendan on weaning from peripheral venoarterial extracorporeal membrane oxygenation in intensive care unit.

BACKGROUND: Few data are available on the impact of levosimendan in refractory cardiogenic shock patients undergoing peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). The aim of this study was to evaluate the impact of levosimendan on VA-ECMO weaning in patients hospitalized in intensive care unit (ICU). METHODS: This retrospective cohort study was conducted in a French university hospital from 2010 to 2017. All patients hospitalized in ICU undergoing VA-ECMO were consecutively evaluated. RESULTS: A total of 150 patients undergoing VA-ECMO were eligible for the study. Thirty-eight propensity-matched patients were evaluated in the levosimendan group and 65 in the non-levosimendan group. In patients treated with levosimendan, left ventricular ejection fraction had increased from 21.5 ± 9.1% to 30.7 ± 13.5% (P < 0.0001) and aortic velocity-time integral from 8.9 ± 4 cm to 12.5 ± 3.8 cm (P = 0.002) 24 h after drug infusion. After propensity score matching, levosimendan was the only factor associated with a significant reduction in VA-ECMO weaning failure rates (hazard ratio = 0.16; 95% confidence interval 0.04-0.7; P = 0.01). Kaplan-Meier survival curves showed that survival rates at 30 days were 78.4% for the levosimendan group and 49.5% for the non-levosimendan group (P = 0.02). After propensity score matching analysis, the difference in 30-day mortality between the two groups was not significant (hazard ratio = 0.55; 95% confidence interval 0.27-1.10; P = 0.09). CONCLUSIONS: Our results suggest that levosimendan was associated with a beneficial effect on VA-ECMO weaning in ICU patients.

Cannula-Related Infection in Patients Supported by Peripheral ECMO: Clinical and Microbiological Characteristics.

Little is known about cannula-related infection (CRI) in patients supported by extracorporeal membrane oxygenation (ECMO). The aim of this study was to assess the incidence, the risk factors, prognosis, and microbiological characteristics of CRI in patients supported by ECMO. This retrospective cohort study was conducted in one intensive care unit (ICU). Among 220 consecutive patients with peripheral ECMO, 39 (17.7%) developed CRI. The incidence of CRI was 17.2 per 1,000 ECMO days. The main isolated microorganisms were Enterobacteriaceae (38%), Staphylococcus spp. (28.2%; 8.5% were methicillin-sensitive Staphylococcus aureus and 19.7% were coagulase-negative staphylococci), and Pseudomonas aeruginosa (18.3%). Bacteremia was present in 23 cases (59.7%). In multivariate analysis, the risk factors for CRI were longer ECMO duration (p = 0.006) and higher Simplified Acute Physiology Score 2 (p = 0.004). Forty-one percentage of patients with CRI needed surgical management of the infected site. Cannula-related infection was not associated with higher in-hospital mortality (p = 0.73), but it was associated with a longer stay in ICU (p < 0.0001) and a longer stay in hospital (p = 0.002). In conclusion, CRI is frequent in patients with ECMO and associated with a longer stay in hospital. Risk factors for CRI were longer ECMO duration and higher Simplified Acute Physiology Score 2. Concomitant bacteremia was frequent (59.7%) and CRI should be strongly investigated in cases of positive blood culture.

Complication patterns in patients undergoing venoarterial extracorporeal membrane oxygenation in intensive care unit: Multiple correspondence analysis and hierarchical ascendant classification.

BACKGROUND: Treatment by venoarterial extracorporeal membrane oxygenation (VA-ECMO) is widely used today, even though it is associated with high risks of complications and death. While studies have focused on the relationship between some of these complications and the risk of death, the relationship between different complications has never been specifically examined, despite the fact that the occurrence of one complication is known to favor the occurrence of others. Our objective was to describe the relationship between complications in patients undergoing VA-ECMO in intensive care unit (ICU) and to identify, if possible, patterns of patients according to complications. METHODS AND FINDINGS: As part of a retrospective cohort study, we conducted a multiple correspondence analysis followed by a hierarchical ascendant classification in order to identify patterns of patients according to main complications (sepsis, thromboembolic event, major transfusion, major bleeding, renal replacement therapy) and in-ICU death. Our cohort of 145 patients presented an in-ICU mortality rate of 50.3%. Morbidity was high, with 36.5% of patients presenting three or more of the five complications studied. Multiple correspondence analysis revealed a cumulative inertia of 76.9% for the first three dimensions. Complications were clustered together and clustered close to death, prompting the identification of four patterns of patients according to complications, including one with no complications. CONCLUSIONS: Our study, based on a large cohort of patients undergoing VA-ECMO in ICU and presenting a mortality rate comparable to that reported in the literature, identified numerous and often interrelated complications. Multiple correspondence analysis and hierarchical ascendant classification yielded clusters of patients and highlighted specific links between some of the complications studied. Further research should be conducted in this area.

Predictors of red blood cell transfusion and its association with prognosis in patients undergoing extracorporeal membrane oxygenation.

PURPOSE: Few data are available on the potential benefits and risks of red blood cell transfusion in patients undergoing extracorporeal membrane oxygenation. The aim of this study was to identify the determinants and prognosis of red blood cell transfusion in patients undergoing extracorporeal membrane oxygenation, with a special focus on biological parameters during extracorporeal membrane oxygenation treatment. METHODS: We conducted a single-center retrospective cohort study including all consecutive patients who underwent extracorporeal membrane oxygenation between January 2010 and December 2015. RESULTS: The 201 evaluated patients received a median of 0.9 [0.5-1.7] units of red blood cell per day. Significant and clinically relevant variables that best correlated with units of red blood cell transfused per day of extracorporeal membrane oxygenation were lower median daily prothrombin time in percentage (Quick) ( t = -0.016, p < 0.0001), higher median daily free bilirubin level ( t = 0.016, p < 0.0001), and lower pH ( t = -2.434, p < 0.0001). In multivariate analysis, red blood cell transfusion was associated with a significantly higher rate of in-intensive care unit mortality (per red blood cell unit increment; adjusted odds ratio: 1.07, 95% confidence interval: 1.02-1.12, p = 0.005). It was also associated with higher rates of acute renal failure ( p = 0.025), thromboembolic complications ( p = 0.0045), and sepsis ( p = 0.015). CONCLUSION: This study suggests that red blood cell transfusion may be associated with a higher mortality rate and with severe complications. However, we cannot conclude a direct causal relationship, as red blood cell transfusion may be only a marker of poor outcome. We recommend that physicians correct acidosis and hemolysis in patients undergoing extracorporeal membrane oxygenation whenever possible.

Extracorporeal membrane oxygenation for cardiogenic shock due to alcoholic cardiomyopathy: a long-term follow-up of 4 cases.

Even though alcoholism is a major health concern, alcoholic cardiomyopathy is a little-known pathology. The exact prevalence remains elusive (20-40% of dilated cardiomyopathy). However, it can lead to dilated cardiomyopathy, heart failure and refractory cardiogenic shock. The literature on cardiogenic shock in alcoholic cardiomyopathy is limited. We report 4 cases of patients with refractory cardiogenic shock due to heavy alcohol consumption, who were treated with venoarterial extracorporeal membrane oxygenation. The evolution was favourable with recovery in 3 patients and the need for heart transplantation in 1 patient. After 3-5 years, all patients are alive, 2 of 4 are sober, all of them are on cardiac follow-up and none of them have presented with a cardiac relapse.

Ten thousand kilometre transfer of cardiogenic shock patients on venoarterial extracorporeal membrane oxygenation for emergency heart transplantation: Cooperation between Reunion Island and Metropolitan France.

BACKGROUND: There is no heart transplantation centre on the French overseas territory of Reunion Island (distance of 10,000 km). The aim of this study was to describe the characteristics of cardiogenic shock adult patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) who were transferred from Reunion Island to mainland France for emergency heart transplantation. METHODS: This retrospective observational study was conducted between 2005 and 2015. The characteristics and outcome of cardiogenic shock patients on VA-ECMO were compared with those of cardiogenic shock patients not on VA-ECMO. RESULTS: Thirty-three cardiogenic shock adult patients were transferred from Reunion Island to Paris for emergency heart transplantation. Among them, 19 (57.6%) needed mechanical circulatory support in the form of VA-ECMO. Median age was 51 (33-57) years and 46% of the patients had ischaemic heart disease. Patients on VA-ECMO presented higher Sequential Organ Failure Assessment score ( p = 0.03). No death occurred during the medical transfer by long flight, while severe complications occurred in 10 patients (30.3%). Incidence of thromboembolic events, severe infectious complications and major haemorrhages was higher in the group of patients on VA-ECMO than in the group of patients not on VA-ECMO ( p <0.01). Seven patients from the VA-ECMO group (36.8%) and six patients from the non-VA-ECMO group (42.9%, p=0.7) underwent heart transplantation after a median delay of 10 (4-29) days on the emergency waiting list. After heart transplantation, one-year survival rates were 85.7% for patients on VA-ECMO and 83.3% for patients not on VA-ECMO ( p=0.91). CONCLUSIONS: This study suggests the feasibility of very long-distance medical evacuation of cardiogenic shock patients on VA-ECMO for emergency heart transplantation, with acceptable long-term results.

Emergence of melioidosis in the Indian Ocean region: Two new cases and a literature review.

Melioidosis is a disease caused by bacteria called B. pseudomallei. Infections can develop after contact with standing water. This disease can reach all the organs and especially the lungs. It is associated with a high mortality rate (up to 50%). Melioidosis is endemic in northern Australia and in Southeast Asia. Nevertheless, B. pseudomallei may be endemic in the Indian Ocean region and in Madagascar in particular, so clinicians and microbiologists should consider acute melioidosis as a differential diagnosis in the Indian Ocean region, in particular from Madagascar.

Case Report: Disseminated Shewanella algae Infection with Meningoencephalitis in a Traveler Secondary to Marine Injury in Madagascar.

Marine microorganisms such as Shewanella spp., Vibrio spp., and Aeromonas spp. can cause sepsis secondary to a wound infection in the context of swimming. These microorganisms are most often susceptible to fluoroquinolones. Here, we report a unique case of Shewanella algae bacteremia associated with meningoencephalitis and disseminated via hematogenous spread secondary to a skin injury. The patient suffered the injury while swimming in saline water during a cruise holiday in Madagascar, and she was initially treated with amoxicillin. The neurological evolution was unsatisfactory. Better knowledge of such infections (and especially of the context in which they occur), as well as greater familiarity with the susceptibility profile of different marine microorganisms would have allowed health professionals to provide presumptive microbiological diagnosis and effective treatment earlier.

Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. DESIGN: A 16-year multicenter retrospective study. SETTING: Fifteen university and nonuniversity ICUs in France. PATIENTS: Patients admitted in ICU for pheochromocytoma crisis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 34 patients with a median age of 46 years (40-54 yr); 65% were males. At admission, the median Sequential Organ Failure Assessment score was 8 (4-12) and median Simplified Acute Physiology Score II 49.5 (27-70). The left ventricular ejection fraction was consistently decreased with a median value of 30% (15-40%). Mechanical ventilation was required in 23 patients, mainly because of congestive heart failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33 of 34 patients. When assayed, urinary metanephrine and catecholamine levels were consistently elevated. Five patients underwent urgent surgery, including two during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34), and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not significantly different between patients managed with versus without extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher severity scores at admission in the extracorporeal membrane oxygenation group. CONCLUSIONS: Mortality is high in pheochromocytoma crisis. Routinely considering this diagnosis and performing abdominal CT in patients with unexplained cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane oxygenation and adrenalectomy should be considered as a therapeutic in most severe cases.

Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock.

BACKGROUND: The therapeutic effect of aminoglycosides is highest and optimal when the peak plasma concentration (C max)/minimal inhibitory concentration (MIC) ratio is between 8 and 10. The French guidelines recommend to use high doses of aminoglycosides for empiric antibiotic therapy in patients suffering from severe sepsis or septic shock. In clinical practice, the recommended target is an amikacin C max between 60 and 80 mg/L, which corresponds to approximately 8 times the MIC breakpoint, as defined by the European Committee on Antimicrobial Susceptibility Testing. The aim of this study was to assess the incidence and impact on mortality of an amikacin concentration between 60 and 80 mg/L in patients suffering from severe sepsis or septic shock. METHODS: This was a prospective observational cohort study conducted in two intensive care units (ICU). Patients receiving amikacin at a loading dose of 30 mg/kg for severe sepsis or septic shock were enrolled in the cohort. The target C max for amikacin was between 60 and 80 mg/L, as recommended by French guidelines (i.e. C max/MIC breakpoint = 8-10). RESULTS: Over the study period, the amikacin C max was <60 mg/L, between 60 and 80 mg/L, and >80 mg/L in 20 (18.2%), 46 (41.8%) and 44 (40%) of the 110 selected patients, respectively. Mortality rate was 40, 28.3 and 56.8% in the groups of patients with C max < 60 mg/L, 60 mg/L < C max < 80 mg/L and C max > 80 mg/L, respectively. Following multivariate analysis, mortality rate was significantly lower in the group of patients with amikacin C max between 60 and 80 mg/L than in the group of patients with amikacin C max > 80 mg/L (P = 0.004). The multivariate analysis also revealed that the factors independently associated with a higher in-ICU mortality rate were age (P = 0.02) and norepinephrine dose (P = 0.0001). CONCLUSIONS: With a loading dose of 30 mg/kg of amikacin, concentration was potentially suboptimal (C max < 60 mg/L) in only 18.2% of patients. The pharmacodynamic target (60 mg/L < C max < 80 mg/L) recommended by French guidelines was reached in 41.8% of patients and was associated with reduced in-ICU mortality. But amikacin overexposure (i.e. C max > 80 mg/L) was frequent and potentially associated with increased mortality.

Obstructive coronary artery disease in patients hospitalized for severe sepsis or septic shock with concomitant acute myocardial infarction.

PURPOSE: It is difficult to differentiate type 1 acute myocardial infarction (AMI) with obstructive coronary artery disease (OCAD) from type 2 AMI in patients admitted for severe sepsis. The aims of this study were to assess the risk factors and prognosis of OCAD in patients admitted to the intensive care unit for severe sepsis with concomitant AMI. MATERIALS AND METHODS: This is a single-center retrospective cohort study including all consecutive patients who were hospitalized for severe sepsis or septic shock between March 2006 and September 2014 and who underwent coronary angiography in the intensive care unit to identify AMI. RESULTS: Overall, 78 (5.5%) of 1418 patients hospitalized for severe sepsis underwent coronary angiography to identify concomitant AMI. Thirty-two patients (41%) had OCAD. Following multivariate analysis, the risk factors of OCAD were peripheral vascular disease (odds ratio [OR] =5.7; 95% confidence interval [CI], 1.1-30.4; P = .042) and at least 2 cardiovascular risk factors (OR = 6.7; 95% CI, 1.9-23.8; P = .003). Obstructive coronary artery disease was associated with a significant mortality increase at 60 days (OR = 8.1; 95% CI, 1.9-30.2; P = .004). CONCLUSIONS: Obstructive coronary artery disease is a poor prognosis factor in patients hospitalized for severe sepsis with concomitant AMI. In this setting, medical treatment should be considered for patients with peripheral vascular disease or with at least 2 cardiovascular risk factors; the need to perform coronary angiography should be considered carefully.

Stress (Tako-tsubo) cardiomyopathy in critically-ill patients.

BACKGROUND: Stress cardiomyopathy (SC) is a transient ventricular dysfunction rarely described in the critical care setting. OBJECTIVE: To evaluate the mechanisms, incidence, treatment and prognosis of SC. METHOD: This is a retrospective observational study of every critically-ill patient admitted to the ICU over a period of two years. RESULTS: Among 1314 patients admitted in the ICU, 20 patients (1.5%) were diagnosed with SC. A total of 249 patients experienced cardiogenic shock, whereas 8% were suffering from SC. SC was suspected because of hemodynamic impairment (80% of cases), ECG modifications (15%) and/or dyspnea (15%). SC was apical (typical Tako-tsubo) in 90% and atypical in 10% of cases. Several mechanisms or conditions may explain the occurrence of SC and are may be combined: catecholamine toxicity (45%), psychological stress, seizures or neurological impairment (35%), non-epicardial coronary ischemia (20%) and left ventricular outflow track (LVOT) obstruction (10%). SC could have indirectly caused death by worsening heart failure in three patients and arrhythmias were seen in 40% of patients. SAPS2, renal impairment, malnutrition, norepinephrine infusion and thrombocytopenia were associated with death in the univariate analysis. Catecholamines were required in 85% and intra-aortic balloon pump in 20% of patients. CONCLUSIONS: SC is a rare reversible cardiac impairment in the critically-ill patient that can induce arrhythmias and cardiogenic shock. The likely mechanisms are combined: catecholamine toxicity, stress or neurological involvement and less frequently ischemia or LVOT obstruction.

CHADS2 and CHA2DS2-VASc scores can predict thromboembolic events after supraventricular arrhythmia in the critically ill patients.

PURPOSE: Prediction of arterial thromboembolic events (ATEs) in relation to supraventricular arrhythmia (SVA) has been poorly investigated in the intensive care unit (ICU). We aimed at evaluating CHADS2 and CHA2DS2-VASc scores to predict SVA-related ATE in the ICU. METHODS: We conducted a prospective observational study including all the patients except those in the postoperative course of cardiac surgery who presented SVA lasting 30 seconds or longer during their ICU stay. We looked for ATE during ICU stay, at the first and sixth month of follow-up after ICU discharge. RESULTS: During the 15-month study period, 108 (12.8%) of 846 ICU patients experienced SVA with 12 SVA-related ATE occurring 6 days (3; 13) (median, 10%-90% percentiles) after SVA onset. In our SVA patients, CHADS2 score was 2 (0; 5), and CHA2DS2-VASc score 3 (0; 7). Both CHADS2 (odds ratio (OR), 1.6 [1.1; 2.4]; P = .01) and CHA2DS2-VASc scores (OR, 1.4 [1.04; 1.8]; P = .03) were significantly associated with ATE onset. However, the most accurate threshold for predicting ATE was CHADS2 score of 4 or higher. Using a multivariate analysis, only patient's history of stroke was associated with ATE onset (OR, 9.2 [2.4; 35]; P = .001). CONCLUSION: CHADS2 and CHA2DS2-VASc scores are predictive of SVA-related thromboembolism in the critically ill patient.

A clinical and EEG scoring system that predicts early cortical response (N20) to somatosensory evoked potentials and outcome after cardiac arrest.

BACKGROUND: Anoxic coma following cardiac arrest is a common problem with ethical, social, and legal consequences. Except for unfavorable somatosensory-evoked potentials (SSEP) results, predictors of unfavorable outcome with a 100% specificity and a high sensitivity are lacking. The aim of the current research was to construct a clinical and EEG scoring system that predicts early cortical response (N20) to somatosensory evoked potentials and 6-months outcome in comatose patients after cardiac arrest. METHODS: We retrospectively reviewed the records of all consecutive patients who suffered cardiac arrest outside our hospital and were subsequently admitted to our facility from November 2002 to July 2006. We scored each case based on early clinical and EEG factors associated with unfavorable SSEPs, and we assessed the ability of this score to predict SSEP results and outcome. RESULTS: Sixty-six patients qualified for inclusion in the cohort. Among them, 34 (52%) had unfavorable SSEP results. At day three, factors independently associated with unfavorable SSEPs were: absence of corneal (14 points) and pupillary (21 points) reflexes, myoclonus (25 points), extensor or absent motor response to painful stimulation (28 points), and malignant EEG (11 points). A score >40 points had a sensitivity of 85%, a specificity of 84%, and a positive predictive value (PPV) of 85% to predict unfavorable SSEP results. A score >88 points had a PPV of 100%, but a sensitivity of 18%. Overall, this score had an area under ROC curves of 0.919. In addition, at day three, a score > 69 points had a PPV of 100% with a sensitivity of 32% to predict death or vegetative state. CONCLUSION: A scoring system based on a combination of clinical and EEG findings can predict the absence of early cortical response to SSEPs. In settings without access to SSEPs, this score may help decision-making in a subset of comatose survivors after a cardiac arrest.

Angiotensin converting enzyme insertion/deletion genetic polymorphism: its impact on renal function in critically ill patients.

OBJECTIVE: Previous clinical studies have suggested an association between the insertion/deletion (I/D) genetic polymorphism of angiotensin converting enzyme and acute or chronic diseases. We aimed to test the prognostic value of the I-allele, which is associated with lower angiotensin converting enzyme activity, on acute kidney injury. DESIGN: Prospective 6-month noninterventional study. SETTING: Intensive care unit of a University Hospital. PATIENTS AND METHODS: One hundred eighty consecutive admitted white patients for an expected intensive care unit stay >48 hr. Angiotensin converting enzyme genetic polymorphism was screened for genotype (I/D polymorphism analysis by polymerase chain reaction amplification) and phenotype (measurement of the circulating rate of angiotensin converting enzyme by spectrophotometry). Acute kidney injury was assessed according to Risk, Injury, Failure, Loss, and End-stage Kidney classification. INTERVENTION: None. RESULTS: II, ID, and DD genotype frequencies were 25%, 48%, and 27%, respectively. II and ID genotypes were associated with lower baseline circulating rates of angiotensin converting enzyme (20 +/- 14 and 22 +/- 18 U/L, respectively, vs. 30 +/- 23 U/L for DD genotype; p = 0.04). Repartition of angiotensin converting enzyme genotypes were different in patients with and without acute kidney injury (p < 0.0001), with greater II genotype proportion in acute kidney injury patients (42% vs. 13% for those without acute kidney injury). After adjustment on the identified prognostic factors, II genotype was independently associated with increased risk of acute kidney injury (adjusted odds ratio, 6.5; 95% confidence interval, 2.4-17.7; p = 0.0002), then death among patients with acute kidney injury (adjusted odds ratio, 1.7; 95% confidence ratio, 1.1-2.6; p = 0.02). CONCLUSION: These data confirm the key role of the renin-angiotensin system to maintain glomerular filtration rate, and highlight an association between a genetic factor and susceptibility to and prognosis of acute kidney disease.

Hyperreninemic hypoaldosteronism syndrome, plasma concentrations of interleukin-6 and outcome in critically ill patients with liver cirrhosis.

OBJECTIVE: To investigate the relation between the adrenal production of gluco- and mineralocorticoids, the inflammatory status and the outcome in critically ill patients with liver cirrhosis. DESIGN: Prospective descriptive study. SETTING: Medical intensive care unit (ICU) in a university hospital. PATIENTS: Fifty consecutive patients with liver cirrhosis. INTERVENTIONS: A corticotropin stimulation test within 12h following ICU admission. Plasma cortisol concentration was measured before and after the test. Renin and aldosterone concentrations, as well as interleukin-6 (IL-6) level to assess the pro-inflammatory status, were measured only before the test. Impaired adrenal function was defined as cortisol response to the test less than 9microg/dl. Hyperreninemic hypoaldosteronism syndrome was defined as basal renin over aldosterone ratio (RRA) higher than 2. MEASUREMENTS AND RESULTS: Forty-one (82%) patients had impaired adrenal function, and 26 patients (52%) presented with RRA > 2. Patients with RRA > 2 exhibited greater disease severity and organ dysfunction scores at baseline, higher levels of serum renin and IL-6, and a greater ICU mortality rate, but risk-adjusted mortality rates were not different between the two groups. Renin and IL-6 plasma concentrations were positively correlated. Finally, in a Cox regression analysis, independent predictors of 30-day mortality were hyperreninemic hypoaldosteronism syndrome, IL-6 higher than 400pg/ml and severe renal failure. CONCLUSIONS: Adrenal dysfunction was common in critically ill cirrhotic patients. Hyperreninemic hypoaldosteronism syndrome was related to a greater pro-inflammatory status and degree of acute organ failure, and was independently associated with a worse prognosis.

Antithrombin supplementation for anticoagulation during continuous hemofiltration in critically ill patients with septic shock: a case-control study.

INTRODUCTION: Acquired antithrombin III (AT) deficiency may induce heparin resistance and premature membrane clotting during continuous renal replacement therapy (CRRT). The purpose of this study was to evaluate the effect of AT supplementation on filter lifespan in critically ill patients with septic shock requiring CRRT. METHODS: We conducted a retrospective case-control analysis based on a 4-year observational study with prospectively collected data in two medical intensive care units in a university hospital. In all, 106 patients with septic shock underwent CRRT during the study period (55 during 2001 to 2002 and 51 during 2003 to 2004). Of these, 78 had acquired AT deficiency (plasma level below 70%) at onset of renal supportive therapy, 40 in the first 2-year period and 38 in the last 2-year period. In the latter intervention period, patients received AT supplementation (50 IU/kg) during CRRT each time that plasma AT activity, measured once daily, fell below 70%. RESULTS: In a case-control analysis of the 78 patients with acquired AT deficiency, groups were similar for baseline characteristics, except in severity of illness as assessed by a higher Simplified Acute Physiology Score (SAPS) II after 2002. In comparison with controls, cases had a significantly greater AT level after AT supplementation, but not at baseline, and a smaller number of episodes of clots, without excess bleeding risk. The median hemofilter survival time was longer in the AT group than in the heparin group (44.5 versus 33.4 hours; p = 0.0045). The hemofiltration dose, assessed by the ratio of delivered to prescribed ultrafiltration, increased during intervention. AT supplementation was independently associated with a decrease in clotting rate, whereas femoral angioaccess and higher SAPS II were independent predictors of filter failure. However, mortality did not differ between periods, in the control period the observed mortality was significantly higher than predicted by the SAPS II score, unlike in the treatment period. CONCLUSION: In sepsis patients requiring CRRT and with acquired AT deficiency, anticoagulation with unfractionated heparin plus AT supplementation prevent premature filter clotting and may contribute to improving outcome, but the cost-effectiveness of AT remains to be determined.