Ratio of carbon dioxide veno-arterial difference to oxygen arterial-venous difference is not associated with lactate decrease after fluid bolus in critically ill patients with hyperlactatemia: results from a prospective observational study.

BACKGROUND: High ratio of the carbon dioxide veno-arterial difference to the oxygen arterial-venous difference (PvaCO2/CavO2) is associated with fluid bolus (FB) induced increase in oxygen consumption (VO2). This study investigated whether PvaCO2/CavO2 was associated with decreases in blood-lactate levels FB in critically ill patients with hyperlactatemia. METHODS: This prospective observational study examined adult patients in the intensive care unit (ICU) with lactate levels > 1.5 mmol/L who received FBs. Blood-lactate levels were measured before and after FB under unchanged metabolic, respiratory, and hemodynamic conditions. The primary outcome was blood-lactate levels after FB. Significant decreases in blood-lactate levels were considered as blood-lactate levels < 1.5 mmol/L or a decrease of more than 10% compared to baseline. RESULTS: The study enrolled 40 critically ill patients, and their median concentration of blood lactate was 2.6 [IQR:1.9 - 3.8] mmol/L. There were 27 (68%) patients with PvaCO2/CavO2 ≥ 1.4 mmHg/ml, and 10 of them had an increase in oxygen consumption (dVO2) ≥ 15% after FB, while 13 (32%) patients had PvaCO2/CavO2 < 1.4 mmHg/ml before FB, and none of them had dVO2 ≥ 15% after FB. FB increased the cardiac index in patients with high and low preinfusion PvaCO2/CavO2 (13.4% [IQR: 8.3 - 20.2] vs. 8.8% [IQR: 2.9 - 17.4], p = 0.34). Baseline PvaCO2/CavO2 was not found to be associated with a decrease in blood lactate after FB (OR: 0.88 [95% CI: 0.39 - 1.98], p = 0.76). A positive correlation was observed between changes in blood lactate and baseline PvaCO2/CavO2 (r = 0.35, p = 0.02). CONCLUSIONS: In critically ill patients with hyperlactatemia, PvaCO2/CavO2 before FB cannot be used to predict decreases in blood-lactate levels after FB. Increased PvaCO2/CavO2 is associated with less decrease in blood-lactate levels.

Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill patients.

BACKGROUND: Transcranial Doppler can detect cerebral perfusion alteration in septic patients. We correlate static Transcranial Doppler findings with clinical signs of sepsis-associated encephalopathy. METHODS: Forty septic patients were examined with Transcranial Doppler on the first and third day of sepsis diagnosis. The pulsatility index (PI) and cerebral blood flow index (CBFi) were calculated by blood velocity in the middle cerebral artery (cm/sec). Patients underwent a daily cognitive assessment with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) test. RESULTS: Twenty-one patients (55%) were found to present confusion. The majority of the patients presented a PI > 1.1 (76%). PI on the first day (but not the third day) could predict a positive CAM-ICU test in septic patients (PI cut-off: 1.3, AUC: 0.905, p < 0.01, sensitivity: 95%, specificity: 88%, AUC: 0.618, p = 0.24). Multivariable analysis showed that PI on the first day is related to a positive CAM-ICU test independent of age and APACHE II score (OR: 5.6, 95% CI: 1.1-29, p = 0.03). A decrease of the PI on the third day was observed in the group that presented initially high PI (>1.3) (2.2 ± 0.71 vs. 1.81 ± 0.64; p = 0.02). On the other hand, an increase in PI was observed in the other patients (1.01 ± 0.15 vs. 1.58 ± 0.57; p < 0.01). On only the first day, the mean blood velocity in the middle cerebral artery and CBFi were found to be lower in those patients with a high initial PI (36 ± 21 vs. 62 ± 28 cm/sec; p < 0.01, 328 ± 101 vs. 581 ± 108; p < 0.01, respectively). CONCLUSIONS: Cerebral perfusion disturbance observed with Transcranial Doppler could explain clinical symptoms of sepsis-associated encephalopathy.

Comparison of dopamine and norepinephrine in the treatment of shock.

BACKGROUND: Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other. METHODS: In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events. RESULTS: The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses). CONCLUSIONS: Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

OBJECTIVES: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. DESIGN: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. SETTING: Two hundred and thirty-three ICUs in 17 countries. PATIENTS: All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. INTERVENTIONS: Patients were randomized to receive IV ART-123 (0.06 mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary endpoint was reduction in mortality. Secondary endpoints included reversal of overt disseminated intravascular coagulation and reduction in disease severity. MEASUREMENTS AND MAIN RESULTS: A total of 750 patients were randomized, nine of whom did not receive the allocated treatment so that 371 patients received ART-123 and 370 received placebo. There were no meaningful differences between the two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8% in the ART-123 group and 21.6% in the placebo group (Cochran-Mantel-Haenszel two-sided p value of 0.273 in favor of ART-123, which met the predefined statistical test for evidence suggestive of efficacy). There were no statistically significant differences in event-free and alive days between the two groups. d-dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART-123 group than in the placebo group. There were no differences between the two groups in organ function, inflammatory markers, bleeding or thrombotic events or in the development of new infections. In post hoc analyses, greatest benefit from ART-123 was seen in patients with at least one organ system dysfunction and an international normalized ratio greater than 1.4 at baseline. CONCLUSIONS: ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

Effective Treatment of Acute Tricyclic Antidepressant Poisoning with Cardiogenic Shock and Severe Rhabdomyolysis Using ECMO and CytoSorb® Adsorber.

BACKGROUND Tricyclic antidepressant (TCA) drugs are a common cause of fatal poisoning because of their cardiotoxic and arrhythmogenic effects. Classic supportive management includes sodium bicarbonate, gastrointestinal chelating agents, and vasopressors. Recently, intravenous lipid emulsion (supported by a low evidence level) has also been used. CASE REPORT We report the case of a 55-year-old woman admitted to our Intensive Care Unit (ICU) with acute imipramine self-poisoning. She arrived at the emergency department 7 hours after imipramine ingestion; she had severe rhabdomyolysis upon admission, with creatine phosphokinase levels at about 52 500 IU/L (normal, <200 IU/L). She quickly developed cardiogenic shock and malign arrhythmia requiring veno-arterial extra corporeal membrane oxygenation (VA-ECMO). Continuous renal replacement therapy (CRRT) with CytoSorb® (CytoSorbents, Monmouth Junction, New York, United Sates of America) was started 19 hours after admission. We performed serial blood measurements of imipramine and its active metabolite desipramine as well as viewing the levels on the CRRT-circuit monitor. Cardiac function improved and ECMO was explanted after 4 days. She also had severe acute respiratory distress syndrome, which resolved spontaneously. The neurologic outcome was favorable despite early myoclonus. The patient regained consciousness on the fifth day. Her clinical evolution was marked by acute ischemia of the lower left limb due to the arterial ECMO cannula. CONCLUSIONS These measurements document the efficacy of the CytoSorb® adsorber in removing a lipophilic drug from a patient's bloodstream. To our knowledge, this is the first published case of CytoSorb® extracorporeal blood purification therapy for acute TCA poisoning.

Torsade de pointes in Kearns-Sayre syndrome.

A 47-year-old woman with Kearns-Sayre syndrome (KSS) and an implanted pacemaker for complete heart block was admitted to the intensive care unit following a cardiac arrest due to ventricular tachycardia (torsade de pointes) in the setting of QT prolongation. Complete heart blocks and ventricular tachycardia are implicated as mechanisms of sudden deaths in KSS; such patients may require pacemaker implantation and implantation of an automatic implantable cardioverter-defibrillator.

Rhabdomyolysis-induced acute renal failure due to itraconazole and simvastatin association.

We present the case of an 82-year-old man admitted to our hospital for muscle weakness. He was under simvastatin 20 mg per day and was given pulse itraconazole therapy 8 days before the onset of symptoms for onychomycosis. He developed severe rhabdomyolysis inducing an acute renal failure necessitating renal replacement therapy. He eventually fully recovered. Given the possible concurrent use of simvastatin and itraconazole, awareness of this potential interaction is clinically important.

Late onset of Aspergillus aortitis presenting as femoral artery embolism following coronary artery bypass graft surgery.

Aspergillus sp. are ubiquitous mould infections and in most patients, the source is presumed to be air-borne infections during surgical procedures. Prevention of these infections requires special attention of ventilation systems in operating rooms. Post-operative aspergillosis occurs mainly in immunocompromised patients as well as those who receive corticosteroids temporarily. We report a case of a 71-year-old immunocompromised patient who developed multiple lower limb embolisms due to Aspergillus niger originating from an aortitis of the ascending aorta nine months following coronary artery bypass graft (CABG) surgery.

Changes in central venous-to-arterial carbon dioxide tension induced by fluid bolus in critically ill patients.

BACKGROUND: In this prospective observational study, we evaluated the effects of fluid bolus (FB) on venous-to-arterial carbon dioxide tension (PvaCO2) in 42 adult critically ill patients with pre-infusion PvaCO2 > 6 mmHg. RESULTS: FB caused a decrease in PvaCO2, from 8.7 [7.6-10.9] mmHg to 6.9 [5.8-8.6] mmHg (p < 0.01). PvaCO2 decreased independently of pre-infusion cardiac index and PvaCO2 changes during FB were not correlated with changes in central venous oxygen saturation (ScvO2) whatever pre-infusion CI. Pre-infusion levels of PvaCO2 were inversely correlated with decreases in PvaCO2 during FB and a pre-infusion PvaCO2 value < 7.7 mmHg could exclude a decrease in PvaCO2 during FB (AUC: 0.79, 95%CI 0.64-0.93; Sensitivity, 91%; Specificity, 55%; p < 0.01). CONCLUSIONS: Fluid bolus decreased abnormal PvaCO2 levels independently of pre-infusion CI. Low baseline PvaCO2 values suggest that a positive response to FB is unlikely.

Outcomes of ICU patients with and without perceptions of excessive care: a comparison between cancer and non-cancer patients.

BACKGROUND: Whether Intensive Care Unit (ICU) clinicians display unconscious bias towards cancer patients is unknown. The aim of this study was to compare the outcomes of critically ill patients with and without perceptions of excessive care (PECs) by ICU clinicians in patients with and without cancer. METHODS: This study is a sub-analysis of the large multicentre DISPROPRICUS study. Clinicians of 56 ICUs in Europe and the United States completed a daily questionnaire about the appropriateness of care during a 28-day period. We compared the cumulative incidence of patients with concordant PECs, treatment limitation decisions (TLDs) and death between patients with uncontrolled and controlled cancer, and patients without cancer. RESULTS: Of the 1641 patients, 117 (7.1%) had uncontrolled cancer and 270 (16.4%) had controlled cancer. The cumulative incidence of concordant PECs in patients with uncontrolled and controlled cancer versus patients without cancer was 20.5%, 8.1%, and 9.1% (p < 0.001 and p = 0.62, respectively). In patients with concordant PECs, we found no evidence for a difference in time from admission until death (HR 1.02, 95% CI 0.60-1.72 and HR 0.87, 95% CI 0.49-1.54) and TLDs (HR 0.81, 95% CI 0.33-1.99 and HR 0.70, 95% CI 0.27-1.81) across subgroups. In patients without concordant PECs, we found differences between the time from admission until death (HR 2.23, 95% CI 1.58-3.15 and 1.66, 95% CI 1.28-2.15), without a corresponding increase in time until TLDs (NA, p = 0.3 and 0.7) across subgroups. CONCLUSIONS: The absence of a difference in time from admission until TLDs and death in patients with concordant PECs makes bias by ICU clinicians towards cancer patients unlikely. However, the differences between the time from admission until death, without a corresponding increase in time until TLDs, suggest prognostic unawareness, uncertainty or optimism in ICU clinicians who did not provide PECs, more specifically in patients with uncontrolled cancer. This study highlights the need to improve intra- and interdisciplinary ethical reflection and subsequent decision-making at the ICU.

Renal replacement therapy is an independent risk factor for mortality in critically ill patients with acute kidney injury.

INTRODUCTION: Outcome studies in patients with acute kidney injury (AKI) have focused on differences between modalities of renal replacement therapy (RRT). The outcome of conservative treatment, however, has never been compared with RRT. METHODS: Nine Belgian intensive care units (ICUs) included all adult patients consecutively admitted with serum creatinine >2 mg/dl. Included treatment options were conservative treatment and intermittent or continuous RRT. Disease severity was determined using the Stuivenberg Hospital Acute Renal Failure (SHARF) score. Outcome parameters studied were mortality, hospital length of stay and renal recovery at hospital discharge. RESULTS: Out of 1,303 included patients, 650 required RRT (58% intermittent, 42% continuous RRT). Overall results showed a higher mortality (43% versus 58%) as well as a longer ICU and hospital stay in RRT patients compared to conservative treatment. Using the SHARF score for adjustment of disease severity, an increased risk of death for RRT compared to conservative treatment of RR = 1.75 (95% CI: 1.4 to 2.3) was found. Additional correction for other severity parameters (Acute Physiology And Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA)), age, type of AKI and clinical conditions confirmed the higher mortality in the RRT group. CONCLUSIONS: The SHARF study showed that the higher mortality expected in AKI patients receiving RRT versus conservative treatment can not only be explained by a higher disease severity in the RRT group, even after multiple corrections. A more critical approach to the need for RRT in AKI patients seems to be warranted.

Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial.

BACKGROUND: There is uncertainty on the effect of different dialysis modalities for the treatment of patients with acute kidney injury (AKI), admitted to the intensive care unit (ICU). This controlled clinical trial performed in the framework of the multicentre SHARF 4 study (Stuivenberg Hospital Acute Renal Failure) aimed to investigate the outcome in patients with AKI, stratified according to severity of disease and randomized to different treatment options. METHODS: This was a multicentre prospective randomized controlled trial with stratification according to severity of disease expressed by the SHARF score. ICU patients were eligible for inclusion when serum creatinine was >2 mg/dL, and RRT was initiated. The selected patients were randomized to intermittent (IRRT) or continuous renal replacement therapy (CRRT). RESULTS: A total of 316 AKI patients were randomly assigned to IRRT (n = 144) or CRRT (n = 172). The mean age was 66 (range 18-96); 59% were male. Intention-to-treat analysis revealed a mortality of 62.5% in IRRT compared to 58.1% in CRRT (P = 0.430). No difference between IRRT and CRRT could be observed in the duration of ICU stay or hospital stay. In survivors, renal recovery at hospital discharge was comparable between both groups. Multivariate analysis, including the SHARF score, APACHE II and SOFA scores for correction of disease severity, showed no difference in mortality between both treatment modalities. This result was confirmed in pre-specified subgroup analysis (elderly, patients with sepsis, heart failure, ventilation) and after exclusion of possible confounders (early mortality, delayed ICU admission). CONCLUSIONS: Modality of RRT, either CRRT or IRRT, had no impact on the outcome in ICU patients with AKI. Both modalities need to be considered as complementary in the treatment of AKI (Clinical Trial: SHARF 4, NCT00322933, http://ClinicalTrials.gov).

High Hemoglobin Level As a Limiting Factor for Extracorporeal Membrane Oxygenation.

We report the case of a 47 year old male who developed acute respiratory distress syndrome after bariatric surgery, requiring a venovenous extracorporeal membrane oxygenation. An inadequate extracorporeal membrane oxygenation output flow was observed, possibly because of severe polycythemia and hyperviscosity. Management with acute normovolemic hemodilution corrected both the biologic and hemodynamic parameters. To our knowledge, this is the first reported case of acute normovolemic hemodilution to improve extracorporeal membrane oxygenation outflow. Clinicians should be aware that polycythemia and hyperviscosity may impair extracorporeal membrane oxygenation support and that acute normovolemic hemodilution may be a safe and efficient procedure to address such matter. The optimal hemoglobin level on extracorporeal membrane oxygenation deserves further investigation.

Cardiogenic Shock after Nifedipine Administration in a Pregnant Patient: A Case Report and Review of the Literature.

We present a case of a 21-year-old Caucasian woman at 27 weeks of pregnancy who was admitted to the obstetric department for pre-term labor. She received 10 mg of nifedipine 4 times in 1 h, according to the internal protocol. Shortly after, she brutally deteriorated with pulmonary edema and hypoxemia requiring transfer to the intensive care unit (ICU) for mechanical ventilation. She finally improved and was successfully extubated after undergoing a percutaneous valvuloplasty of the mitral valve. This case illustrates a severe cardiogenic shock after administration of nifedipine for premature labor in a context of unknown rheumatic mitral stenosis. Nifedipine induces a reflex tachycardia that reduces the diastolic period and thereby precipitates pulmonary edema in case of mitral stenosis. This case emphasizes the fact that this drug may be severely harmful and should never be used before a careful physical examination and echocardiography if valvular heart disease is suspected.

Cerebral perfusion alterations and cognitive decline in critically ill sepsis survivors.

INTRODUCTION: We investigated the association between cerebral perfusion perturbations in sepsis with possible cognitive decline (CD) after patients' discharge from the intensive care unit (ICU). METHODS: We studied 28 patients with sepsis and Lawton's Instrumental Activities of Daily Living scale (IADL) scores ≥5 who were discharged from a university ICU institution. We evaluated cerebral circulatory parameters (pulsatility index (PI) and cerebral blood flow index (CBFi) was calculated based on the measured velocity of the middle cerebral artery. Use of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) test was performed daily, and either the Mini Mental State Examination test (MMSE) or Clock Drawing test was performed at ICU discharge. CD was categorized as persistent coma, positive CAM-ICU test at discharge, MMSE <24, or an abnormal Clock test. RESULTS: Patients had a median pre-ICU IADL score of 6.3 (95% CI 5.9-6.7). Fourteen patients (50%) had CD at discharge. Two were in persistent coma despite sepsis resolution. Information recall was the most affected mental function of the other 12 patients. Only on the first day, patients with CD had higher PI and lower CBFi compared to those without CD (2.2 ± 0.7 vs. 1.4 ± 0.5, p = 0.02; 363 ± 170 vs. 499 ± 133, p = 0.03, respectively). Multivariable analysis revealed delirium, but not PI, as an independent prognostic factor for CD (OR: 29.62, 95%CI 1.91-458.01, p = 0.01). CONCLUSION: Delirium, but not cerebral perfusion alterations, is an independent risk factor for cognitive impairment in septic patients who were discharged from the ICU.

Injection of agitated saline to detect recirculation with transthoracic echocardiography during venovenous extracorporeal oxygenation: A pilot study.

PURPOSE: We assessed the security and efficiency of intravenously injected agitated saline in conjunction with transthoracic echocardiography to identify recirculation in patients supported with a venovenous extracorporeal membrane oxygenation (VV ECMO) device. MATERIALS AND METHODS: We injected agitated saline 4 consecutive times separated by an interval of 5 minutes in 2 patients supported by VV ECMO. In both patients, the drainage cannula was placed in the left femoral vein, and the return cannula was placed in the right internal jugular vein. Echocardiography was performed during the injection and until the bubbles disappeared. The security of the method was assessed by evaluating the mechanical function of the ECMO and the efficiency of the oxygenator. The value of this method was assessed by visualizing the increase of inferior vena cava's echogenicity as well as by measuring the time required for this change to occur after the injection of agitated saline at different ECMO output levels. RESULTS: We did not observe any change in ECMO, oxygenation function, or the hemodynamic status of patients after the 4 injections of agitated saline. The echogenicity of the inferior vena cava increased more rapidly as the ECMO's output increased. The recirculation phenomenon was noted even with low levels of ECMO output (<2 L/min). CONCLUSIONS: Transthoracic echocardiography in conjunction with agitated saline administration may be a safe and easily applicable method to evaluate a recirculation phenomenon in patients supported with VV ECMO.