Measuring resting energy expenditure during extracorporeal membrane oxygenation: preliminary clinical experience with a proposed theoretical model.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe respiratory failure. Indirect calorimetry (IC) is a safe and non-invasive method for measuring resting energy expenditure (REE). No data exist on the use of IC in ECMO-treated patients as oxygen uptake and carbon dioxide elimination are divided between mechanical ventilation and the artificial lung. We report our preliminary clinical experience with a theoretical model that derives REE from IC measurements obtained separately on the ventilator and on the artificial lung. METHODS: A patient undergoing veno-venous ECMO for acute respiratory failure due to bilateral pneumonia was studied. The calorimeter was first connected to the ventilator and oxygen consumption (VO2 ) and carbon dioxide transport (VCO2 ) were measured until steady state was reached. Subsequently, the IC was connected to the membrane oxygenator and similar gas analysis was performed. VO2 and VCO2 values at the native and artificial lung were summed and incorporated in the Weir equation to obtain a REEcomposite . RESULTS: At the ventilator level, VO2 and VCO2 were 29.5 ml/min and 16 ml/min. VO2 and VCO2 at the artificial lung level were 213 ml/min and 187 ml/min. Based on these values, a REEcomposite of 1703 kcal/day was obtained. The Faisy-Fagon and Harris-Benedict equations calculated a REE of 1373 and 1563 kcal/day. CONCLUSION: We present IC-acquired gas analysis in ECMO patients. We propose to insert individually obtained IC measurements at the native and the artificial lung in the Weir equation for retrieving a measured REEcomposite .

Measured versus calculated resting energy expenditure in critically ill adult patients. Do mathematics match the gold standard?

BACKGROUND: Indirect calorimetry (IC) is considered to be the standard method for estimating energy requirements in intensive care unit (ICU) patients. Hence, most ICU clinicians still rely on various mathematical formulas to calculate caloric requirements in their patients. We assessed whether measurements obtained by IC reached agreement with the results of such commonly used equations. METHODS: Retrospective study in consecutively hospitalized patients in a mixed medico-surgical adult ICU. Resting energy expenditure (REE) was measured by IC in all patients as a standard procedure within our routine nutritional care planning and simultaneously calculated from 10 distinct predictive equations. IC was performed with the VmaxTM Encore 29n calorimeter (VIASYS Healthcare Inc, Yorba Linda, CA). Bland-Altman plots and regression analysis were used to assess agreement between measured and calculated REE. RESULTS: The study included 259 critically ill patients: 161 subjects (62%) met final analysis criteria (age 63 ± 16 years; 58% males). Measured REE was 1571 ± 423.5 kcal/24 h with VO2 0.23 ± 0.06 L/min and VCO2 0.18 ± 0.05 L/min. Calculated values correlated very weakly with IC-derived measurements. Only the Swinamer equation and the Penn State 2010 reached an R² > 0.5. Widely used formulas in daily ICU practice such as the adjusted Harris Benedict, Faisy-Fagon, and ESICM '98 statement equations, reached R² values of respectively only 0.44, 0.49, and 0.41. Calculation resulted in under- as well as overestimation of REE. Global formulas reached no acceptable correlation in elderly or obese critically ill patients. CONCLUSION: In critically ill adult patients, measured REE poorly correlated with calculated values, regardless what formula was used. Our findings underscore the important role of IC to adequately estimate energy requirements in this particularly frail population.

Do-not-resuscitate orders in the critically ill patient--an observational study with special emphasis on withholding of renal replacement therapy.

We examined the process, consequences and impact of writing a Do-Not-Resuscitate (DNR) order in a cohort of critically-ill ICU patients. Special emphasis was given to the DNR order including withholding renal replacement therapy. A DNR code was mainly written in the first week following ICU admission and more often given to medical, older and sicker patients. Patients never actively participated in the decision and in only half of the cases the DNR order was discussed with relatives. Mortality of all patients studied was 21% of whom 67% died with a DNR order. In our population, the final in-hospital mortality rate of DNR-coded patients was 100%, because the DNR status was ordered when the patients were already very sick. DNR-coded patients died after a longer mean length of ICU stay than patients without a code. Withholding renal replacement therapy was commonly added to the DNR order even if renal failure either was not present or never developed.

Sepsis-related acute kidney injury: a protective effect of drotrecogin alpha (activated) treatment?

BACKGROUND: Drotrecogin alpha activated (DrotAA) is licensed for treatment of patients with severe sepsis and organ failure. Among the latter, acute kidney injury (AKI), defined as the persistence of oligo-anuria following adequate resuscitation, is one of the most apprehended. We conducted a prospective, observational, and controlled study to test the hypothesis that DrotAA beneficially affected the evolution and outcome of AKI, complicating acute sepsis-induced cardiopulmonary failure. METHODS: Forty-six patients were studied. Thirty subjects received standard treatment for sepsis without DrotAA. In the remaining 16 patients, DrotAA was added as a continuous infusion of 24 microg/kg/h for 96 h. RESULTS: Mean age, causes of sepsis, and severity/organ failure scores were comparable between patients treated with or without DrotAA. Mortality at 28 days was high and comparable between both treatment groups (56% vs. 69%, DrotAA vs. no DrotAA; P=0.5). When oligo-anuria was present at the start of the study, it persisted during treatment in all patients, with no significant difference between groups. Both treatment groups presented with baseline mean daily fractional excretion of sodium values >2% that remained high during the observation period, regardless of whether DrotAA was given or not. Kidney histology showed a preserved renal architecture with tubular necrosis in all specimens. Similar glomerular, tubulo-interstitial, and vascular alterations were present in both treatment groups. CONCLUSION: In this small cohort of patients with severe sepsis who received adjuvant DrotAA treatment, no effect on urine output, tubular function, or mortality could be demonstrated.

Soluble fiber reduces the incidence of diarrhea in septic patients receiving total enteral nutrition: a prospective, double-blind, randomized, and controlled trial.

BACKGROUND AND AIMS: Attempts to control enteral nutrition associated diarrhea in the critically ill tube-fed patient by implementing feeding formulas enriched with fiber were mostly unsuccessful. Recently, it was shown that enteral feeding containing soluble partially hydrolyzed guar decreased the incidence of diarrhea in a cohort of non-critically ill medicosurgical patients. We investigated whether this type of enteral feed could also influence stool production in patients with severe sepsis, a population at risk for developing diarrhea. METHODS: The study was double-blind. Patients with severe sepsis and septic shock were consecutively enrolled and at random received either an enteral formula supplemented with 22 g/l partially hydrolyzed guar or an isocaloric isonitrogenous control feed without fiber. All patients were mechanically ventilated and treated with catecholamines and antibiotics. Enteral feeding was provided through a nasogastric tube for a minimum of 6 days. A semiquantitative score based on stool volume and consistency was used for daily assessment of diarrhea. RESULTS: 25 patients fulfilled the criteria for data analysis. Soluble fiber was administered in 13 of them. The two groups were well-matched for gender, age, disease severity, cause of sepsis, laboratory parameters, total feeding days and time to reach nutritional goals. The mean frequency of diarrhea days was significantly lower in patients receiving fiber than in those on standard alimentation (8.8+/-10.0 % vs 32.0+/-15.3 %; P=0.001). The whole group of fiber-fed patients had less days with diarrhea per total feeding days (16/148 days (10.8%) vs 46/146 days (31.5%); P<0.001) and a lower mean diarrhea score (4.8+/-6.4 vs 9.4+/-10.2; P<0.001). The type of enteral diet did not influence sepsis-related mortality and duration of stay in the intensive care unit. CONCLUSION: Total enteral nutrition supplemented with soluble fiber is beneficial in reducing the incidence of diarrhea in tube-fed full-resuscitated and mechanically ventilated septic patients.

A prospective, open, single blind, randomized study comparing four analgesics in the treatment of peripheral injury in the emergency department.

The efficacy of four analgesics, distinct concerning analgesic power and mechanism of action, was evaluated for pain relief in patients suffering from single peripheral injury. Patients were randomly allocated to receive either propacetamol (the pro-drug of paracetamol) 20 mg/kg i.v., piritramide 0.25 mg/kg i.m., tramadol 1 mg/kg i.v. or diclofenac 1 mg/kg i.v. Pain scores were measured by the patient using the visual analogue scale (VAS) and by an observer using a 4-point verbal rating scale (VRS). Cardiorespiratory variables and side effects were recorded. One hundred and sixty patients were included, 131 completed the study. Groups matched for demography and baseline pain levels. In general pain scores decreased with time. No significant differences were found between groups at any particular time point. VAS scores were significantly (p < 0.02) lower than baseline scores 30 minutes after injection in all treatment groups except for the piritramide group where significance (p < 0.01) was reached after 60 minutes. VRS score analysis showed a similar trend although significances differed. In the piritramide group significantly more side effects were noted than in the other groups (p < 0.05). We conclude that intravenous propacetamol, tramadol and diclofenac are equally efficacious for emergency analgesic treatment of single peripheral trauma.

Liver perfusion and hepatocellular inflammatory response in sepsis.

Sepsis is characterized by disturbances in liver perfusion and alterations in intrahepatic cellular functions and interactions. This provokes structural and functional liver damage as well as hepatocellular activation that is believed to perpetuate the immuno-inflammatory response. Changes in hepatic perfusion during sepsis are still poorly understood due to the heterogeneity of septic animal models and the difficult accessibility of the hepatic circulation in humans. Sinusoidal blood flow is severely compromised during sepsis due to a decline in perfused sinusoidal area in association with a decrease in sinusoidal flow velocity. Imbalances in the production of nitric oxide may account for these (micro) circulatory disorders. Interactions between liver macrophages, activated endothelial cells and hepatocytes determine the intensity of inflammation and contribute to initial liver damage. Hepatocellular injury is then enhanced by attracted and invading neutrophils. The management of hepatic dysfunction during sepsis is largely supportive and based on prevention and vigorous resuscitation including early nutritional support and adequate oxygenation. Interestingly, experimental studies suggest that pharmacological interventions with significant hemodynamic effects, such as dobutamine and nitric oxide synthase inhibitors, may adversely affect the liver during the septic process.

Chronic thromboembolic pulmonary hypertension and vascular transformation of the lymph node sinuses.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease often not recognized until it is far advanced. Medical management does not reverse the effects of the disease, nor does it prevent its progression. Pulmonary thromboendarterectomy is the preferred treatment. We present the case of a patient in whom CTEPH was mistaken for an interstitial lung disease with mediastinal lymph node enlargement. The mediastinal lymph node enlargement was due to vascular transformation of the lymph node sinuses (VTS). This is an unusual case of chronic thromboembolic pulmonary hypertension with vascular transformation of the lymph node sinuses.

Splenic abscess with Clostridium novyi bacteraemia and sepsis.

Splenic abscess is an uncommon entity and usually results in the death of the patient when left undiagnosed. A case is presented where bacteraemia with an anaerobic Gram-positive bacillus was associated with splenic abscess. Despite treatment with splenectomy and antibiotics the patient developed a multiple organ dysfunction syndrome (MODS) and died. Of particular interest was the isolation of Clostridium novyi type A from the blood in a patient without gas gangrene but with splenic suppuration.

Early electrocardiographic signs in acute massive pulmonary embolism.

As a result of the increasing accuracy in diagnosing acute pulmonary embolism by isotopic ventilation-perfusion scintigraphy and pulmonary arterial angiography, the electrocardiographic changes associated with acute cor pulmonale are being abandoned as a diagnostic tool for this life-threatening disease. Nevertheless, certain electrocardiographic findings can raise the suspicion of pulmonary embolism. In our view the electrocardiogram does have some merits in the emergency work-up of a patient with a high suspicion of pulmonary embolism. In this case report we emphasize the importance of the electrocardiographic findings which forwarded the diagnosis of pulmonary embolism. Hence the necessary invasive diagnostic and therapeutic measures, i.e. pulmonary arterial angiography and thrombolytic therapy, can be taken immediately after admission to the emergency department.

Intermittent hemodialysis in critically ill patients with multiple organ dysfunction syndrome is associated with intestinal intramucosal acidosis.

OBJECTIVE: Conventional intermittent hemodialysis in the critically ill patient can be associated with hemodynamic and respiratory instability. Intermittent hemodialysis induced arterial hypotension might be detrimental. We therefore studied the influence of intermittent hemodialysis on systemic and regional oxygen transport in critically ill patients. DESIGN: Prospective descriptive study. SETTING: Medical/surgical 24-bed intensive care unit in a university hospital. PATIENTS: Eleven critically ill patients admitted to the intensive care unit (APACHE III score: 82 +/- 12) and developing multiple organ dysfunction syndrome with acute renal failure. All patients were mechanically ventilated and hemodynamically stable with inotropic support. Systemic oxygen transport variables were calculated, and arterial blood lactate concentration was measured before, during, and after intermittent hemodialysis. Tonometer PCO2 was measured using a tonometer, and arterial-tonometer CO2 gap was used as an indicator of intestinal intramucosal acidosis. RESULTS: Intermittent hemodialysis induced an increase in calculated systemic oxygen consumption (P < 0.01). During intermittent hemodialysis there was a significantly higher need of inotropic support (P < 0.05) to maintain arterial blood pressure, cardiac index, and calculated systemic arterial oxygen delivery. The arterial-tonometer CO2 gap increased significantly during and after the procedure. CONCLUSION: In critically ill patients with multiple organ dysfunction syndrome intermittent hemodialysis induces an increase in oxygen consumption. Despite higher inotropic support to maintain systemic calculated oxygen delivery intestinal intramucosal acidosis occurs during intermittent hemodialysis and may even persist after the procedure is terminated.

N-methyl-D-aspartate receptor activation by guanidinosuccinate but not by methylguanidine: behavioural and electrophysiological evidence.

Levels of methylguanidine (MG) and guanidinosuccinate (GSA) are known to be highly increased in uraemic patients. In the present work, the effects of these uraemic guanidino compounds on the excitatory amino acid system were investigated in vivo and in vitro. It was found that convulsions induced by intracerebroventricular GSA injection in mice were antagonized by N-methyl-D-aspartate (NMDA) receptor blockade, whereas those induced by MG were not significantly altered. Application of GSA (between 25 and 10,000 microM) to mouse spinal cord neurones in primary dissociated cell cultures, evoked depolarizing, inward whole-cell currents in a dose-dependent fashion and with reversal potential at 0 mV; MG did not produce such effects. GSA-induced whole-cell currents were caused by NMDA receptor activation since NMDA receptor antagonists (2-amino-5-phosphonovalerate, Mg2+ and ketamine) blocked GSA-evoked whole-cell currents completely and reversibly, whereas co-application of a non-NMDA receptor antagonist (6-cyano-7-nitroquinoxaline-2,3-dione) did not affect GSA-induced current. Evoked field potentials in CA1 region of rat hippocampal slices were completely abolished by GSA, and this effect was antagonized by NMDA receptor blockade. All data were consistent with selective agonist action of GSA upon the NMDA-type glutamate receptor. In view of the results presented here, it should be examined whether NMDA receptors contribute to the neurological complications of renal failure through GSA-induced inappropriate or excessive activation of NMDA receptors.

Combined intoxication with a tricyclic antidepressive agent and a neuroleptic.

We report the case of a patient who co-ingested a tricyclic antidepressant (2500 mg of doxepin) and a neuroleptic drug (3500 mg of prothipendyl). Following overdose either agent can affect the central nervous and cardiovascular systems, inducing arrhythmias, conduction disturbances and hypotension. The presented case illustrates that a combined overdose of tricyclic antidepressants and neuroleptics enhances the possible toxic effects of each drug and especially the risk for adverse cardiac events. The clinical features and management of this combined intoxication are discussed. Treatment with sodium bicarbonate readily corrected a potentially life-threatening cardiac arrhythmia and is therefore suggested to be imperative in the treatment of these cases.

Epidural abscess: case report and review of the literature.

Spinal epidural abscess is an uncommon site of infection, resulting in back pain, fever, weakness and loss of sensibility. These signs should suggest the diagnosis, and quick confirmation by MRI should be performed. Immediate surgical decompression and antibiotherapy is necessary, because this is the base of a possible successful functional recovery. Empiric therapy consisting of high dose of penicillinase-resistant antibiotics is advised because most often an epidural abscess is caused by Staphylococcus aureus. However, because other bacteria can be involved, an aminoglycoside or a cephalosporin should be added to the empiric treatment, until the results of the cultures are known. When diagnosis and therapy are delayed, permanent paralysis and death are common.

Reversible cardiac failure in an adolescent after prolonged exposure to carbon monoxide.

We describe the case of an adolescent who developed a severe but fully reversible cardiac dysfunction with low blood levels of carboxy haemoglobin (COHb = 10%) after a prolonged exposure to carbon monoxide. A 15-year-old male was admitted with a Glasgow Coma Scale of 8/15 with suspected postictal state and postanoxic encephalopathy. The cardiorespiratory failure which he developed soon after admission mandated mechanical ventilation, inotropic support and ultimately left ventricular support by intra-aortic balloon counterpulsation. The cardiac dysfunction was documented by radionuclide imaging and echocardiography. The patient fully recovered without neurological deficit. A low blood COHb concentration is a poor safety indicator since high tissue levels of accumulated carbon monoxide can be associated with coma and fulminant cardiorespiratory failure requiring advanced life support facilities.