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.

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.

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.

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.

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.

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.

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.

Outcome of elderly patients with circulatory failure.

PURPOSE: The proportion of elderly patients admitted to the ICU is increasing. Mortality rates are known to increase with age but the impact of age on outcomes after circulatory shock has not been well defined. METHODS: We performed a secondary analysis of data from a large randomized trial comparing the effects of dopamine and norepinephrine on outcome in the ICU. Patients were separated into not old (<75 years), old (75-84 years), and very old (≥85 years). RESULTS: Of the 1,679 patients included in the initial trial, 1,651 had sufficient age data available: 1,157 (70%) were not old, 410 (25%) were old, and 84 (5%) were very old. There were minor differences among the age groups in the APACHE II score calculated without the age component (not old, 17 ± 9; old, 18 ± 9; very old, 19 ± 9; p = 0.047), but SOFA scores were similar (not old, 9 ± 4; old, 9 ± 3; very old, 9 ± 3; p = 0.76). Mortality rates were higher in old and very old patients at 28 days, at hospital discharge, and after 6 and 12 months. Most very old patients were dead at 6 (92%) and 12 months (97%). Mortality rates increased with age in all types of shock. Using multivariable analysis, the risk of death was higher in very old patients as compared to not old (adjusted OR 0.33, 95% CI 0.2-0.56, p < 0.001). CONCLUSIONS: Ageing is independently associated with higher mortality rates in patients with circulatory failure, whatever the etiology. By 1 year after admission, most patients 85 years of age and older were dead.

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.

The 'normobaric oxygen paradox': does it increase haemoglobin?

BACKGROUND: A novel approach to increasing erythropoietin (EPO) using oxygen (O2) (the 'normobaric oxygen paradox') has been reported in healthy volunteers. We investigated whether the EPO increase is sufficient to induce erythropoiesis by comparing two protocols of O2 administration. METHODS: We compared the effect of daily versus alternate days 100% O2, breathed for 30 minutes, on haemoglobin concentrations during a 12-day period. Nine subjects underwent the two protocols six weeks apart. RESULTS: We observed a significant increase in haemoglobin (as a percentage of baseline) in the alternate-days group compared to the daily group and to baseline after four days (105.5 ∓ 5.7 % vs. 99.6 ∓ 3.3 % difference from baseline; P < 0.01). At the end of the experimental period, haemoglobin values increased significantly compared to baseline in both groups. There was a significant percentage rise in reticulocyte count in the alternate-days group compared to the daily group (182 ∓ 94 % vs. 93 ∓ 34 %; P < 0.001). CONCLUSION: The normobaric oxygen paradox seems effective in increasing haemoglobin in non-anaemic, healthy volunteers, providing sufficient time is allowed between O2 applications. The exact time interval is not clearly defined by this study but should probably be at least or greater than two days. Further studies are needed to define more precisely clinical applications in the use of O2 as a pharmaceutical agent.

Is there a correlation between circulating levels of citrulline and intestinal dysfunction in the critically ill?

OBJECTIVE: The aim of this study was to assess the correlation between plasma citrulline and Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, survival, inflammation (C-reactive protein [CRP]), inotrope use, serum levels of prealbumin and albumin, and renal failure in the critically ill patient. METHODS: This prospective observational single-center controlled study included 91 adult patients over a 2-year period. Inclusion criteria were patients staying in the intensive care unit for >48 hours. Patients' renal status was categorized as those with a glomerular filtration rate (GFR) >60 mL/min without renal support, a GFR >60 mL/min with renal support, a GFR <60 mL/min without renal support, and a GFR <60 mL/min with renal support. Plasma citrulline concentrations were categorized into 3 groups: low (0-15 µmol/L), medium (16-35 µmol/L), and high (>36 µmol/L). The relationship between the recorded parameters and these different cut-off values of plasma citrulline concentrations was analyzed. RESULTS: Ninety-one patients (34% female and 66% male) with a mean (SD) age of 69.3 (11.9) years, a mean (SD) body mass index of 24.8 (5.34) kg/m(2), a mean (SD) APACHE II score of 22.4 (7.92), a mean (SD) SOFA score of 8 (4.4), and a mean (SD) plasma citrulline of 21.7 (13.1) µmol/L were enrolled. Only patients with intestinal dysfunction had low plasma citrulline level <15 µmol/L (P = .014). No correlations between serum levels of CRP, albumin, or prealbumin; renal failure; inotrope use; SOFA score; and APACHE II score were found with plasma citrulline level. CONCLUSION: Low plasma citrulline levels in patients correlate well with intestinal dysfunction.

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.

A fatal case of cutaneous adverse drug-induced toxic epidermal necrolysis associated with severe rhabdomyolysis.

Toxic epidermal necrolysis represents an immunologic reaction to a foreign antigen and is most often caused by drugs. Atorvastatin, a blood cholesterol-lowering agent, is a recognized cause of rhabdomyolysis; while naproxen, a widely used nonsteroidal anti-inflammatory drug, is a known cause of photo-induced skin lesions. We report the first fatal case of drug-induced toxic epidermal necrolysis associated with severe muscle necrosis due to the use of a nonsteroidal anti-inflammatory drug and a statin with very high levels of creatine phosphokinase leading to acute kidney injury, disseminated intravascular coagulation, and complete skin necrosis leading to death.

Successful treatment of Chlamydophila pneumoniae acute respiratory distress syndrome with extracorporeal membrane oxygenator: a case report and diagnostic review.

INTRODUCTION: Chlamydophila pneumoniae is a respiratory pathogen known to infect the upper and lower respiratory tracts. Infection severity can range from sub-clinical pulmonary infection to acute respiratory distress syndrome. CASE PRESENTATION: A previously healthy 62-year-old Caucasian man was admitted to our hospital for acute respiratory failure. Serum samples obtained every week starting from the day of admission showed clear-cut seroconversion for C. pneumoniae antibodies. All other cultures obtained during the first days of hospitalization were negative. Despite maximal ventilatory support (high positive end expiratory pressure, fraction of inspired oxygen of 1.0, nitric oxide inhalation, neuromuscular blocking agents and prone positioning), our patient remained severely hypoxemic, which led us to initiate an extracorporeal membrane oxygenation treatment. Extracorporeal membrane oxygenation and hemodiafiltration were withdrawn on day 12. Our patient was extubated on day 18 and discharged from our Intensive Care Unit on day 20. He went home a month later. CONCLUSION: We describe the first published case of acute respiratory distress syndrome due to C. pneumoniae infection successfully treated by extracorporeal membrane oxygenation, a very useful tool in this syndrome. A quick and specific method for the definite diagnosis of Chlamydophila infection should be developed.

Influence of bedside blood insulin measurement on acute coronary syndrome pathways.

BACKGROUND: The aim of the study was to evaluate the influence of blood insulin measurements on acute coronary syndrome (ACS) pathways. METHODS: All patients admitted to the emergency department within 12 months for acute, retrosternal, constrictive chest pain lasting for more than 30 minutes; cardiogenic pulmonary edema; electrocardiogram ST changes; and echographic alterations were included. The study parameters were clinical (age, sex, blood pressure, presence of pulmonary rales and gallop), including classic laboratory tests associated with troponin T, blood insulin levels, and hemoglobin A1C, and echographic values. These were taken on admission and throughout hospital stay. All patients underwent a coronary angiography for ACS diagnosis confirmation as well as treatment intention. RESULTS: Sixty patients were included in the study. Abnormal blood insulin levels were present on admission in 47% of the population. Blood insulin level was significantly correlated to thrombolysis in myocardial infarction coronary perfusion score (Spearman Rank, 0.55, P < 0.0001). Abnormal insulinemia was normalized with reperfusion. Insulin was administered essentially to the 16 patients with hypoinsulinemia. Patients with hypoinsulinemia seem to have the most severe coronary lesions and highest Killip score. CONCLUSIONS: In ACS, insulin levels are altered in half of the patients. After the investigators noted its tight correlation with the thrombolysis in myocardial infarction coronary flow score, its determination could be important in ACS for triggering emergency coronary angiography for percutaneous coronary intervention. This could modify the critical pathways of ACS patients in the emergency department.