The fluid management of adults with severe malaria.

Fluid resuscitation has long been considered a key intervention in the treatment of adults with severe falciparum malaria. Profound hypovolemia is common in these patients and has the potential to exacerbate the acidosis and acute kidney injury that are independent predictors of death. However, new microvascular imaging techniques have shown that disease severity correlates more strongly with obstruction of the microcirculation by parasitized erythrocytes--a process termed sequestration. Fluid loading has little effect on sequestration and increases the risk of complications, particularly pulmonary edema, a condition that can develop suddenly and unpredictably and that is frequently fatal in this population. Accordingly, even if a patient is clinically hypovolemic, if there is an adequate blood pressure and urine output, there may be little advantage in infusing intravenous fluid beyond a maintenance rate of 1 to 2 mL/kg per hour. The optimal agent for fluid resuscitation remains uncertain; significant anemia requires blood transfusion, but colloid solutions may be associated with harm and should be avoided. The preferred crystalloid is unclear, although the use of balanced solutions requires investigation. There are fewer data to guide the fluid management of severe vivax and knowlesi malaria, although a similar conservative strategy would appear prudent.

Paracetamol induced skin blood flow and blood pressure changes in febrile intensive care patients: An observational study.

OBJECTIVE: To determine the relationship between paracetamol administration and skin blood flow (skBF) and blood pressure (BP) in critically ill patients treated for fever. DESIGN: Prospective, observational study. SETTING: Intensive care units of university teaching hospital. PATIENTS: 29 adults (17 males and 12 females), aged 58±15 years treated with enteral or intravenous paracetamol for fever. APACHE II score was 17.2±8.3 and admission classifications were 41% medical (n=12), 31% surgical (n=9), and 28% neurological intervention (n=8). Thirty healthy afebrile volunteers were also studied after ingesting 1g paracetamol. MEASUREMENTS AND MAIN RESULTS: Temperature, BP and skBF (laser Doppler flowmetry perfusion units) were recorded 15 min prior to administration of paracetamol, at administration (T0) and then for every 15 min for 60 min. Cutaneous vascular conductance (CVC=skBF/mean arterial pressure) was calculated. Thirty data sets were recorded from 29 patients. Temperature at T0 was 38.7±0.6°C. BP decreased over the study period whilst skBF and CVC increased (repeated measured ANOVA, p<.05). Systolic BP decreased significantly (p<.01) at all post-administration times and was 90±13% of T0 at 60 min. CVC was 128±48% of T0 at 60 min. Systolic BP fell by a clinically significant amount (≥15%) in 17 patients (59%) and hypotension was treated during 33% (n=10) of the observation periods. BP and skBF did not change significantly in afebrile volunteers. CONCLUSIONS: Paracetamol induced increases in skBF consistent with its antipyretic action and may be associated with significant falls in BP in the critically ill.

Deleterious effect of nitric oxide inhibition in chronic hepatopulmonary syndrome.

On the basis of limited experimental and clinical studies, increased activity of the vasodilatory nitric oxide-cyclic guanosine monophosphate pathway is considered to play a key role in the pathogenesis of hepatopulmonary syndrome. We report a 46-year-old woman with Child-Pugh class C cirrhosis and progressive dyspnoea for 12 months. Investigations revealed elevated circulating concentrations of nitric oxide metabolites and exhaled nitric oxide levels, an hyperdynamic circulation with low systemic vascular resistance and mean arterial pressure, a large right to left intrapulmonary shunt fraction on radiolabelled macroaggregated albumin perfusion scanning, positive contrast-enhanced echocardiography, reduced diffusion capacity of carbon monoxide, hypoxaemia and orthodeoxyia, all in keeping with severe hepatopulmonary syndrome. Sequential inhibition of the nitric oxide-cyclic guanosine monophosphate pathway using curcumin (diferuloylmethane), terlipressin and methylene blue was associated with substantial improvements in vascular tone and the hyperdynamic circulation. No improvement, however, in the intrapulmonary shunt was demonstrated. Both hypoxaemia and orthodeoxia were substantially, reproducibly and reversibly worsened with all three treatments. Our findings argue against the contention that intrapulmonary shunting and impairment in arterial oxygenation in hepatopulmonary syndrome are necessarily the consequence of on-going, nitric oxide-cyclic guanosine monophosphate-mediated vasodilatation, at least in the chronic stage, and, given the possibility of substantial worsening of pulmonary oxygen exchange, suggest that inhibition of the nitric oxide-cyclic guanosine monophosphate pathway should be avoided in this setting.

An Australian experience with the molecular adsorbents recirculating system (Mars).

The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin-bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi-organ failure in patients with acute liver failure and acute-on-chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/beta-hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in-hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi-organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.

A novel method for insertion of post-pyloric feeding tubes at the bedside without endoscopic or fluoroscopic assistance: a prospective study.

OBJECTIVE: To assess a novel method, adapted from already published literature, for bedside placement of nasojejunal feeding tubes using erythromycin, air insufflation of the stomach and continuous ECG guidance. DESIGN AND SETTING: Prospective study in a tertiary teaching hospital. PATIENTS AND PARTICIPANTS: 40 consecutive patients who required enteral nutrition and mechanical ventilation for at least 48 h. INTERVENTIONS: Erythromycin (200 mg) was administered intravenously 30 min prior to the insertion of the feeding tube. The post-pyloric feeding tube was then inserted into the stomach and 500 ml air insufflated. Stomach ECG was performed, and during further insertion of the tube the QRS complex was continuously monitored for a change in polarity, suggesting passage across the midline through the pylorus. At the end of the procedure aspirate was obtained from the feeding tube and checked for alkaline pH. Exact tube position was determined by abdominal radiography. MEASUREMENTS AND RESULTS: In 88% of cases the feeding tubes were post-pyloric, with a median time to insertion of 15 min (range 7-75). No major complications were seen in 52 attempts. Change in QRS polarity had 94% sensitivity in predicting post-pyloric tip placement. Of the 32 alkaline pH aspirates 31 were post-pyloric. CONCLUSIONS: This procedure is safe, effective and could be performed in a short time period within the confines of the intensive care unit without endoscopic assistance.

Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study.

OBJECTIVE: Although intra-abdominal hypertension (IAH) can cause dysfunction of several organs and raise mortality, little information is available on the incidence and risk factors for IAH in critically ill patients. This study assessed the prevalence of IAH and its risk factors in a mixed population of intensive care patients. DESIGN: A multicentre, prospective 1-day point-prevalence epidemiological study conducted in 13 ICUs of six countries. INTERVENTIONS: None. PATIENTS: Ninety-seven patients admitted for more than 24 h to one of the ICUs during the 1-day study period. METHODS: Intra-abdominal pressure (IAP) was measured four times (every 6 h) by the bladder pressure method. Data included the demographics, medical or surgical type of admission, SOFA score, etiological factors such as abdominal surgery, haemoperitoneum, abdominal infection, massive fluid resuscitation, and ileus and predisposing conditions such as hypothermia, acidosis, polytransfusion, coagulopathy, sepsis, liver dysfunction, pneumonia and bacteraemia. RESULTS: We enrolled 97 patients, mean age 64+/-15 years, 57 (59%) medical and 40 (41%) surgical admission, SOFA score of 6.5+/-4.0. Mean IAP was 9.8+/-4.7 mmHg. The prevalence of IAH (defined as IAP 12 mmHg or more) was 50.5 and 8.2% had abdominal compartment syndrome (defined as IAP 20 mmHg or more). The only risk factor significantly associated with IAH was the body mass index, while massive fluid resuscitation, renal and coagulation impairment were at limit of significance. CONCLUSION: Although we found a quite high prevalence of IAH, no risk factors were reliably associated with IAH; consequently, to get valid information about IAH, IAP needs to be measured.

Nitric-oxide-lowering effect of terlipressin in decompensated cirrhosis: comparison to the molecular adsorbent recirculating system and correlation with clinical status.

Systemic vasodilatation and arterial hypotension, refractory to adrenergic vasopressors, portend a poor prognosis in patients with decompensated cirrhosis. The production of large amounts of nitric oxide, consequent to endotoxin-induced tumour necrosis factor (TNF)-alpha-mediated upregulation of inducible nitric oxide synthase (iNOS), has been suggested to be central to this phenomenon. Terlipressin has recently been shown in an animal model of cirrhosis to suppress endotoxin-induced TNF-alpha-mediated upregulation of iNOS, thereby preventing overproduction of nitric oxide and restoring normal vascular tone. We present the first evidence that this effect of terlipressin may also occur clinically, in a patient with Child-Pugh class C cirrhosis, endotoxaemia, a raised circulating TNF-alpha concentration, and marked systemic vasodilatation with refractory arterial hypotension. Beneficial effects of terlipressin on circulating nitrate and nitrite concentrations, haemodynamic status, plasma renin levels and indocyanine green clearance were comparable to those of the molecular adsorbent recirculating system (MARS). Our findings suggest that terlipressin may be the vasopressor agent of choice in patients with decompensated cirrhosis and provide a rationale for combination terlipressin and MARS therapy when the therapeutic response to either treatment alone is suboptimal.

Equipment review: the molecular adsorbents recirculating system (MARS).

The molecular adsorbents recirculating system (MARS) is a form of artificial liver support that has the potential to remove substantial quantities of albumin-bound toxins that have been postulated to contribute to the pathogenesis of liver cell damage, haemodynamic instability and multi-organ failure in patients with acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF). These toxins include fatty acids, bile acids, tryptophan, bilirubin, aromatic amino acids and nitric oxide. Data from controlled clinical trials are limited so far. One of two studies performed on small numbers of patients with AoCLF suggest a survival benefit, but no controlled data are available in the ALF setting. Our preliminary experience with MARS therapy, instituted late in the clinical course of five patients with severely impaired liver function, including three with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease, indicates some clinical efficacy. However, the overall survival rate (1 of 5; 20%) remained poor. More data obtained from larger cohorts of patients enrolled in randomised controlled studies will be required in both the AoCLF and ALF settings to identify categories of liver failure patients who might benefit most from MARS treatment, to ascertain the most appropriate timing of intervention and to determine the overall impact on outcome, including cost-effectiveness.

Assessment of the clinical utility of an ultrasonic monitor of cardiac output (the USCOM) and agreement with thermodilution measurement.

OBJECTIVE: To assess the clinical utility of an ultrasonic monitor of cardiac output (USCOM), its reliability in tracking cardiac output (CO) changes and agreement with thermodilution (TD) measurements of CO. DESIGN: Prospective comparison study. SETTING AND PARTICIPANTS: 55 adults undergoing thermodilution (TD) CO monitoring in a cardiothoracic or general intensive care unit between December 2006 and December 2007. MAIN OUTCOME MEASURES: USCOM and TD measurements of CO on two occasions in each patient were compared by Bland-Altman analysis for bias and limit of agreement. A mean percentage error <30% was considered acceptable. Per cent change in cardiac index (CI) was determined by each method. Doppler profiles obtained by the USCOM were assessed against an ideal standard ("acceptable"). RESULTS: 55 patients had measurements on 110 occasions, but Doppler waveforms were not obtained on 18 of these (16%), leaving 39 patients with paired comparisons for analysis (including 27 men; mean age, 64.7 [SD, 14.5] years). Mean TD CI was 3.4 +/-1.0L/min/m(2) (range, 2.0-6.0L/min/m(2)). The bias was 0.6L/min/m(2) (95% confidence limits [CLs], 0.4-0.8 L/min/m(2)), and the mean percentage error was 56% (95% CLs, 45%-65%). Twenty-two Doppler profiles (28%) were classed as acceptable; the mean percentage error for these was 62% (95% CLs, 38%-65%). On 15/19 occasions (74%) where TD CI changed > 15%, USCOM CI also changed >15%, but three of these changes (16%) were in the opposite direction. USCOM CI changed >15% on 9/20 occasions (45%) when TD CI did not. CONCLUSIONS: Poor agreement with TD and a substantial rate of failure to obtain an USCOM measurement suggest that this device is unsuitable as a monitoring tool in intensive care.

Heparin-induced thrombosis with a normal platelet count.

Heparin is commonly used in the intensive care unit for preventing and treating thromboembolic disease. One of its more significant complications is heparin-induced thrombocytopenia (HIT), an immune-mediated disorder which can provoke an extreme prothrombotic state. We describe an unusual presentation of HIT, where thrombocytopenia was absent.

Postsurgical infections are reduced with specialized nutrition support.

OBJECTIVE: The objective was to examine the relationship between pre-, peri-, and postoperative specialized nutritional support with immune-modulating nutrients and postoperative morbidity in patients undergoing elective surgery. METHODS: Studies were identified by searching MEDLINE, review article bibliographies, and abstracts and proceedings of scientific meetings. All randomized clinical trials in which patients were supplemented by the IMPACT formula before and/or after elective surgery and the clinical outcomes reported were included in the meta-analysis. Seventeen studies (n=2,305), 14 published (n=2,102), and 3 unpublished (n=203), fulfilled the inclusion criteria. Ten studies (n=1,392) examined the efficacy of pre- or perioperative IMPACT supplementation in patients undergoing elective surgery, whereas 7 (n=913) assessed postoperative efficacy. Fourteen of the studies (n=2,083) involved gastrointestinal (GI) surgical patients. Postoperative complications, mortality, and length of stay in hospital (LOS) were major outcomes of interest. RESULTS: IMPACT supplementation, in general, was associated with significant (39%-61%) reductions in postoperative infectious complications and a significant decrease in LOS in hospital by an average of 2 days. The greatest improvement in postoperative outcomes was observed in patients receiving specialized nutrition support as part of their preoperative treatment. In GI surgical patients, anastomotic leaks were 46% less prevalent when IMPACT supplementation was part of the preoperative treatment. CONCLUSION: This study identifies a dosage (0.5-1 l/day) and duration (supplementation for 5-7 days before surgery) of IMPACT that contributes to improved outcomes of morbidity in elective surgery patients, particularly those undergoing GI surgical procedures. The cost effectiveness of such practice is supported by recent health economic analysis. Findings suggest preoperative IMPACT use for the prophylaxis of postoperative complications in elective surgical patients.

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study.

OBJECTIVE: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. DESIGN: Multiple-center, prospective epidemiologic study. SETTING: Fourteen intensive care units in six countries. PATIENTS: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. CONCLUSIONS: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.