Meta-Analysis of Post-Intubation Hypotension: A Plea to Consider Circulation First in Hypovolemic Patients.

Hypovolemic patients can develop postintubation hypotension (PIH). Our objective is to review the literature regarding PIH and the association with mortality. We searched MEDLINE from inception to February 2018. A meta-analysis was performed to assess the effect of PIH on mortality. The results of the meta-analysis were reported in forest plots of the estimated effects of the included studies with a 95 per cent confidence interval. Heterogeneity was evaluated using the I² test, which corresponded to low (I² < 25%), medium (I² = 25-75%), and high (I² > 75%) heterogeneity. We identified 243 records. Four studies were included in the meta-analysis. The studies reported 2044 patients with 36.8 per cent (n = 753) developing PIH. Data indirectly reflecting the hemodynamic status were available in three studies (n = 1117 patients). Overall mortality was 24.6 per cent (n = 503) and was significantly higher in patients that developed PIH [mortality, n (%): PIH = 250/753 (33.2%) vs 253/1291 (19.6%), P < 0.001]. Patients that develop PIH have an increased mortality. Considering a targeted resuscitation in hypovolemic patients is pivotal to minimize PIH.

Hypertonic saline in critical illness - A systematic review.

INTRODUCTION: The optimal approach to fluid management in critically ill patients is highly debated. Fluid resuscitation using hypertonic saline was used in the past for more than thirty years, but has recently disappeared from clinical practice. Here we provide an overview on the currently available literature on effects of hypertonic saline infusion for fluid resuscitation in the critically ill. METHODS: Systematic analysis of reports of clinical trials comparing effects of hypertonic saline as resuscitation fluid to other available crystalloid solutions. A literature search of MEDLINE and the Cochrane Controlled Clinical trials register (CENTRAL) was conducted to identify suitable studies. RESULTS: The applied search strategy produced 2284 potential publications. After eliminating doubles, 855 titles and abstracts were screened and 40 references retrieved for full text analysis. At total of 25 scientific studies meet the prespecified inclusion criteria for this study. CONCLUSION: Fluid resuscitation using hypertonic saline results in volume expansion and less total infusion volume. This may be of interest in oedematous patients with intravascular volume depletion. When such strategies are employed, renal effects may differ markedly according to prior intravascular volume status. Hypertonic saline induced changes in serum osmolality and electrolytes return to baseline within a limited period in time. Sparse evidence indicates that resuscitation with hypertonic saline results in less perioperative complications, ICU days and mortality in selected patients. In conclusion, the use of hypertonic saline may have beneficial features in selected critically ill patients when carefully chosen. Further clinical studies assessing relevant clinical outcomes are warranted.

Mortality rates are lower in SIAD, than in hypervolaemic or hypovolaemic hyponatraemia: Results of a prospective observational study.

OBJECTIVE: Hyponatraemia is associated with increased mortality, but the mortality associated specifically with SIAD is not known. We hypothesized that mortality in SIAD was elevated, but that it was less than in hypervolaemic (HEN) or hypovolaemic (HON) hyponatraemia. DESIGN: Mortality rates are presented as risk ratios (RR),with 95% confidence intervals (CI), and compared to normonatraemic controls (NN). METHODS: Prospective, single centre, noninterventional study of all patients with hyponatraemia (≤130 mmol/L) admitted to hospital. RESULTS: A total of 1323 admissions with hyponatraemia were prospectively evaluated and 1136 contemporaneous NN controls. 431(32.6%) hyponatraemic patients had HON, 573(43.3%) had SIAD and 275(20.8%) patients had HEN. In patient mortality was higher in hyponatraemia than NN (9.1% vs 3.3%, P<.0001). The RRs for in-hospital mortality compared to NN were: SIAD, 1.76 (95% CI 1.08-2.8, P=.02), HON 2.77 (95% CI 1.8-4.3, P<.0001) and HEN, 4.9 (95% CI 3.2-7.4, P<.0001). The mortality rate was higher in HEN (RR 2.85; 95% CI 1.86-4.37, P<.0001) and in HON, (RR 1.6; 95% CI 1.04-2.52; P=.03), when compared to SIAD. The Charlson Comorbidity Index was lower in SIAD than in eunatraemic patients (P<.0001). 9/121(7.4%) patients died with plasma sodium <125 mmol/L and 4(3.3%) with plasma sodium <120 mmol/L. However, 69/121(57%) patients died with a plasma sodium above 133 mmol/L. CONCLUSIONS: We confirmed higher all-cause mortality in hyponatraemia than in NN. Mortality was higher in SIAD than in normonatraemia and was not explained on the basis of co-morbidities. Mortality was higher in HON and HEN than in SIAD. Mortality rates reported for all-cause hyponatraemia in the medical literature are not applicable to SIAD.

How safe is gelatin? A systematic review and meta-analysis of gelatin-containing plasma expanders vs crystalloids and albumin.

Gelatin is a widely used synthetic colloid resuscitation fluid. We undertook a systematic review and meta-analysis of adverse effects in randomized and nonrandomized studies comparing gelatin with crystalloid or albumin for treatment of hypovolemia. Multiple databases were searched systematically without language restrictions until August 2015. We assessed risk of bias of individual studies and certainty in evidence assessment by the Grading of Recommendations Assessment, Development, and Evaluation approach. Sixty studies were eligible, including 30 randomized controlled trials, 8 nonrandomized studies, and 22 animal studies. After gelatin administration, the risk ratios were 1.15 (95% confidence interval, 0.96-1.38) for mortality, 1.10 (0.86-1.41) for requiring allogeneic blood transfusion, 1.35 (0.58-3.14) for acute kidney injury, and 3.01 (1.27-7.14) for anaphylaxis. Well-performed nonrandomized trials found increased rates of hospital mortality and acute kidney injury or renal replacement therapy in the gelatin intervention periods. Between 17% and 31% of administered gelatin was taken up extravascularly. The mean crystalloid-to-colloid ratio was 1.4. Gelatin solutions increase the risk of anaphylaxis and may be harmful by increasing mortality, renal failure, and bleeding possibly due to extravascular uptake and coagulation impairment. Until well-designed randomized controlled trials show that gelatin is safe, we caution against the use of gelatins because cheaper and safer fluid alternatives are available.

Early dynamic left intraventricular obstruction is associated with hypovolemia and high mortality in septic shock patients.

INTRODUCTION: Based on previously published case reports demonstrating dynamic left intraventricular obstruction (IVO) triggered by hypovolemia or catecholamines, this study aimed to establish: (1) IVO occurrence in septic shock patients; (2) correlation between the intraventricular gradient and volume status and fluid responsiveness; and (3) mortality rate. METHOD: We prospectively analyzed patients with septic shock admitted to a general ICU over a 28-month period who presented Doppler signs of IVO. Clinical characteristics and hemodynamic parameters as well as echocardiographic data regarding left ventricular function, size, and calculated mass, and left ventricular outflow Doppler pattern and velocity before and after fluid infusions were recorded. RESULTS: During the study period, 218 patients with septic shock were admitted to our ICU. IVO was observed in 47 (22%) patients. Mortality rate at 28 days was found to be higher in patients with than in patients without IVO (55% versus 33%, p < 0.01). Small, hypercontractile left ventricles (end-diastolic left ventricular surface 4.7 ± 2.1 cm(2)/m(2) and ejection fraction 82 ± 12%), and frequent pseudohypertrophy were found in these patients. A rise ≥12% in stroke index was found in 87% of patients with IVO, with a drop of 47% in IVO after fluid infusion. CONCLUSION: Left IVO is a frequent event in septic shock patients with an important correlation with fluid responsiveness. The mortality rate was found to be higher in these patients in comparison with patients without obstruction.

The rationale for microcirculatory guided fluid therapy.

PURPOSE OF REVIEW: The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac output to improve microcirculatory perfusion and tissue oxygenation. Observation of the microcirculation using handheld microscopes gives insight into the nature of convective and diffusive defect in hypovolemia. The purpose of this article is to introduce a new platform for hemodynamic-targeted fluid therapy based on the correction of tissue and microcirculatory perfusion assumed to be at risk during hypovolemia. RECENT FINDINGS: Targeting systemic hemodynamic targets and/or clinical surrogates of hypovolemia gives inadequate guarantee for the correction of tissue perfusion by fluid therapy especially in conditions of distributive shock as occur in inflammation and sepsis. Findings are presented, which support the idea that only clinical signs of hypovolemia associated with low microcirculatory flow can be expected to benefit from fluid therapy and that fluid overload causes a defect in the diffusion of oxygen transport. SUMMARY: We hypothesized that the optimal amount of fluid needed for correction of hypovolemia is defined by a physiologically based functional microcirculatory hemodynamic platform where convection and diffusion need to be optimized. Future clinical trials using handheld microscopes able to automatically evaluate the microcirculation at the bedside will show whether such a platform will indeed optimize fluid therapy.

Reporting bias in trials of volume resuscitation with hydroxyethyl starch.

The possibility of renal damage by hydroxyethyl starch has become the focus of intensive dispute based on the findings of published large trials. The aim of this narrative review is to analyze outcome reporting bias in the literature on volume resuscitation, focusing on selective outcome reporting in published randomized and observational trials with "modern" hydroxyethyl starch as therapeutic intervention. Three recent publications claimed to confirm renal safety of hydroxyethyl starch 130/0.4 for indications in severe sepsis, trauma, and critical illness, respectively. Selective outcome reporting was identified in these studies including underreporting of side effects and change of primary study outcomes. In conclusion, selective outcome reporting bias is identified in recent publications of clinical trials on volume resuscitation with HES.

Flat inferior vena cava: indicator of poor prognosis in trauma and acute care surgery patients.

Flat inferior vena cava (IVC) on ultrasound examination has been shown to correlate with hypovolemic status. We hypothesize that a flat IVC on limited echocardiogram (LTTE) performed in the emergency room (ER) correlates with poor prognosis in acutely ill surgical patients. We conducted a retrospective review of all patients undergoing LTTE in the ER from September 2010 until June 2011. IVC diameter was estimated by subxiphoid window. Flat IVC was defined as diameter less than 2 cm. Fat IVC was defined as diameter greater than 2 cm. Need for intensive care unit admission, blood transfusion requirement, mortality, and need for emergent operation between patients with flat versus Fat IVC were compared. One hundred one hypotensive patients had LTTE performed in the ER. Average age was 38 years. Admission diagnosis was blunt trauma (n = 80), penetrating trauma (n = 13), acute care surgery pathology (n = 7), and burn (n = 1). Seventy-four patients had flat IVC on initial LTTE. Compared with those with fat IVC, flat patients were found have higher rates of intensive care unit admission (51.3 vs 14.8%; P = 0.001), blood transfusion requirement (12.2 vs 3.7%), and mortality (13.5 vs 3.7%). This population also underwent emergent surgery on hospital Day 1 more often (16.2 vs 0%; P = 0.033). Initial flat IVC on LTTE is an indicator of hypovolemia and a predictor of poor outcome.

Human albumin solution for resuscitation and volume expansion in critically ill patients.

BACKGROUND: Human albumin solutions are used for a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, such as in burns and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register (searched 31 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (Ovid) (1948 to week 3 May 2011), EMBASE (Ovid) (1980 to Week 21 2011), CINAHL (EBSCO) (1982 to May 2011), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to May 2011), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to May 2011), PubMed (www.ncbi.nlm.nih.gov/sites/entrez/) (searched 10 June 2011, limit: last 60 days). Reference lists of trials and review articles were checked, and authors of identified trials were contacted. SELECTION CRITERIA: Randomised controlled trials comparing albumin or PPF with no albumin or PPF or with a crystalloid solution in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 38 trials meeting the inclusion criteria and reporting death as an outcome. There were 1,958 deaths among 10,842 trial participants.For hypovolaemia, the relative risk of death following albumin administration was 1.02 (95% confidence interval (CI) 0.92 to 1.13). This estimate was heavily influenced by the results of the SAFE trial, which contributed 75.2% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.93 (95% CI 1.28 to 6.72) and for hypoalbuminaemia the relative risk was 1.26 (95% CI 0.84 to 1.88). There was no substantial heterogeneity between the trials in the various categories (Chi(2) = 26.66, df = 31, P = 0.69). The pooled relative risk of death with albumin administration was 1.05 (95% CI 0.95 to 1.16). AUTHORS' CONCLUSIONS: For patients with hypovolaemia, there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as saline. There is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia. The possibility that there may be highly selected populations of critically ill patients in which albumin may be indicated remains open to question. However, in view of the absence of evidence of a mortality benefit from albumin and the increased cost of albumin compared to alternatives such as saline, it would seem reasonable that albumin should only be used within the context of well concealed and adequately powered randomised controlled trials.

Human albumin solution for resuscitation and volume expansion in critically ill patients.

BACKGROUND: Human albumin solutions are used for a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, such as in burns and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register (searched 31 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (Ovid) (1948 to week 3 May 2011), EMBASE (Ovid) (1980 to Week 21 2011), CINAHL (EBSCO) (1982 to May 2011), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to May 2011), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to May 2011), PubMed (www.ncbi.nlm.nih.gov/sites/entrez/) (searched 10 June 2011, limit: last 60 days). Reference lists of trials and review articles were checked, and authors of identified trials were contacted. SELECTION CRITERIA: Randomised controlled trials comparing albumin or PPF with no albumin or PPF or with a crystalloid solution in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 38 trials meeting the inclusion criteria and reporting death as an outcome. There were 1,958 deaths among 10,842 trial participants.For hypovolaemia, the relative risk of death following albumin administration was 1.02 (95% confidence interval (CI) 0.92 to 1.13). This estimate was heavily influenced by the results of the SAFE trial, which contributed 75.2% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.93 (95% CI 1.28 to 6.72) and for hypoalbuminaemia the relative risk was 1.26 (95% CI 0.84 to 1.88). There was no substantial heterogeneity between the trials in the various categories (Chi(2) = 26.66, df = 31, P = 0.69). The pooled relative risk of death with albumin administration was 1.05 (95% CI 0.95 to 1.16). AUTHORS' CONCLUSIONS: For patients with hypovolaemia, there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as saline. There is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia. The possibility that there may be highly selected populations of critically ill patients in which albumin may be indicated remains open to question. However, in view of the absence of evidence of a mortality benefit from albumin and the increased cost of albumin compared to alternatives such as saline, it would seem reasonable that albumin should only be used within the context of well concealed and adequately powered randomised controlled trials.

B-type natriuretic peptide and interdialytic fluid retention are independent and incremental predictors of mortality in hemodialysis patients.

AIM: Management of fluid homeostasis remains a major challenge in hemodialysis patients. We aimed to establish whether the cardiac strain marker B-type natriuretic peptide (BNP) could help to identify hypervolemic patients at increased risk of death. METHODS: BNP levels were determined before dialysis in the entire HD population at our institution (n = 57). IDWG and BNP were stratified above or below 1.5 kg or the median value, respectively. All patients were prospectively followed for 35 months. The influence of IDWG and BNP on mortality was assessed with a Cox proportional hazards model, adjusted for each other, as well as for demographics, comorbidities, cardiac function, residual diuresis, dialysis duration and efficiency and complications of renal failure. RESULTS: Median BNP was 303 (135 - 692) and 21 (36%) patients displayed an average IDWG below 1.5 kg. During follow up a total of 25 (44%) patients died, 5 (26%) in the low IDWG group and 20 (53%) in the high IDWG group (adjusted hazard ratio (adjusted HR) 5.31 95% CI (1.47 - 19.1), p = 0.011). In the low BNP group 7 (25%) patients died and in the high BNP Group 18 (62%) patients died (adjusted HR 3.53 95 CI (1.37 - 9.09), p = 0.009). When both factors were considered simultaneously, patients with low BNP and low IDWG had an 11 times lower risk of death compared to patients with high BNP and high IDWG (HR. 0.08 95% CI (0.01 - 0.6129, p = 0.015). CONCLUSIONS: BNP and IDWG are independent and incremental predictors of mortality in HD patients. These findings suggest that BNP guided fluid management could improve survival in these patients.

Early vasopressor use in critical injury is associated with mortality independent from volume status.

BACKGROUND: Complications of excessive crystalloid after critical injury have increased interest in vasopressor support. However, it is hypothesized that vasopressor use in patients who are under-resuscitated is associated with death. We performed this study to determine whether volume status is associated with increased mortality in the critically injured exposed to early vasopressors. METHODS: The intensive care unit database at a Level I center was queried for all adult admissions surviving for >24 hours from January 1, 2001, to December 31, 2008. Patients with spinal cord injury and severe traumatic brain injury were excluded. The vasopressor group [Vaso (+)] was exposed to dopamine, epinephrine, phenylephrine, norepinephrine, or arginine vasopressin within 24 hours of admission. Demographic and injury data were studied including intensive care unit admission central venous pressure. Hypovolemia [Hypov (+)] was considered an admission central venous pressure ≤8 mm Hg. The Vaso (+) group was analyzed to determine whether Hypov (+) was independently associated with death. RESULTS: Of 1,349 eligible patients, 26% (351) were Vaso (+). Mortality was 43.6% (153) in the Vaso (+) versus 4.2% (42) in the Vaso (-) group (17.60 [12.10-25.60], <0.01). Vasopressor exposure was associated with death independent of injury severity. In Vaso (+) patients, Hypov (+) was not associated with mortality, whereas Emergency Department admission Glasgow Coma Scale ≤8 and multiple vasopressor use were. CONCLUSIONS: Vasopressor exposure early after critical injury is independently associated with death and mortality is increased regardless of fluid status. Although it is not advisable to withhold support with impending cardiovascular collapse, use of any vasopressor during ongoing resuscitation should be approached with extreme caution regardless of volume status.

Severe controlled hemorrhage resuscitation with small volume poloxamer 188 in sedated miniature swine.

BACKGROUND: The surfactant poloxamer 188 (P188) has been shown to improve survival following hemorrhage. This study used P188 as a small volume resuscitation product in a sedated, sexually mature, male miniature swine severe hemorrhage model for potential improvement in rate and time of survival. METHODS: Fourteen swine were anesthetized, catheterized for hemorrhage and resuscitation and allowed to recover from anesthesia. The animals were sedated and hemorrhaged 60% of estimated blood volume (∼39 mlkg(-1)) exponentially over 1h. Following hemorrhage the animals were treated with either 1.33 mlkg(-1) of P188 (150 mgml(-1); 7 swine) or the P188 citrate vehicle (7 swine) given as an i.v. infusion over 2 min without additional resuscitation fluids. The data were compared with control data from sedated swine similarly hemorrhaged, but with no resuscitation (untreated; n=16). RESULTS: Median (95% CI) survival time for the untreated control swine was 55.8 (36.5-86) min with a 6% survival at 180 min. Median survival time of 161 (80-180) min for the P188 swine was significantly greater than control (p=0.0186), whereas the citrate vehicle median survival time of 91 (32-180) min was not significantly different from control or P188. At the survival target time of 180 min, survival rates were not significantly different among the three groups. TEG data from swine demonstrated anti-coagulant properties of P188. This was confirmed with human blood ex vivo. CONCLUSION: In the presence of severe controlled hemorrhage, P188 improved median survival time. However, retardation of blood clotting raises concerns as to its use in the presence of uncontrolled hemorrhage.

[Clinical application of the plasma substitutes in patients with postoperative complications after surgeries for brain meningioma].

The issues on optimization of the restoration treatment of patients, suffering the brain meningioma, were discussed, basing on analysis of 498 observations. Tactics of the patients management in noncomplicated, complicated and severe course of postoperative period is adduced. The indices of survival and lethality, peculiarities of the infusion therapy were analyzed. The role of plasm-restituting preparations was demonstrated in complicated course of postoperative period. Rational complex approach to the restoration measures and intensive therapy conduction promotes the treatment efficacy raising, the patients fair quality of life securing in the brain meningioma in postoperative period.

Phase II trial of isotonic fluid resuscitation in Kenyan children with severe malnutrition and hypovolaemia.

BACKGROUND: Children with severe malnutrition who develop shock have a high mortality. Contrary to contemporaneous paediatric practice, current guidelines recommend use of low dose hypotonic fluid resuscitation (half-strength Darrows/5% dextrose (HSD/5D). We evaluated the safety and efficacy of this guideline compared to resuscitation with a standard isotonic solution. METHODS: A Phase II randomised controlled, safety and efficacy trial in Kenyan children aged over 6 months with severe malnutrition and shock including children with severe dehydration/shock and presumptive septic shock (non-diarrhoeal shock). Eligible children were randomised to HSD/5D or Ringer's Lactate (RL). A maximum of two boluses of 15 ml/kg of HSD/5D were given over two hours (as recommended by guidelines) while those randomised to RL received 10 ml/kg aliquots half hourly (maximum 40 ml/kg). Primary endpoint was resolution of shock at 8 and 24 hours. Secondary outcomes included resolution of acidosis, adverse events and mortality. RESULTS: 61 children were enrolled: 41 had shock and severe dehydrating diarrhoea, 20 had presumptive septic shock; 69% had decompensated shock. By 8 hours response to volume resuscitation was poor with shock persisting in most children:-HSD/5D 15/22 (68%) and RL14/25 (52%), p = 0.39. Oliguria was more prevalent at 8 hours in the HSD/5D group, 9/22 (41%), compared to RL-3/25 (12%), p = 0.02. Mortality was high, HSD/5D-15/26(58%) and RL 13/29(45%); p = 0.42. Most deaths occurred within 48 hours of admission. Neither pulmonary oedema nor cardiogenic failure was detected. CONCLUSIONS: Outcome was universally poor characterised by persistence of shock, oliguria and high case fatality. Isotonic fluid was associated with modest improvement in shock and survival when compared to HSD/5D but inconclusive due to the limitations of design and effectiveness of either resuscitation strategy. Although isotonic fluid resuscitation did not result in cardiogenic heart failure, as previously feared, we conclude that the modest volumes used and rate of infusion were insufficient to promptly correct shock. The adverse performance of the recommended fluid resuscitation guideline for severe malnutrition should prompt clinical investigation of isotonic fluids for resuscitation of compensated shock, defining rate and volumes required to inform future guidelines. TRIAL REGISTRATION: The trial is registered as ISCRTN: 61146418.

Developmental changes in catecholamine requirement, volume load and corticosteroid supplementation in premature infants born at 22 to 28 weeks of gestation.

BACKGROUND: Due to circulatory instability, premature infants require volume loads, catecholamines and steroid supplementation to improve mortality and neurodevelopmental outcome. However, a complete quantitative analysis concerning the relationship between supplementation and gestational age, especially in infants born at 22 to 24 weeks of gestation, is lacking. AIM: To investigate whether less mature infants need higher doses of catecholamine, volume loads and steroid, and whether those who require higher doses have poorer outcome. STUDY DESIGN: A retrospective, observational study was performed at a tertiary center in a university setting. Among the consecutive 221 premature infants born at 22 to 28 weeks of gestation, we selected 108 infants who had no apparent pathological conditions other than prematurity. Catecholamines, volume loads and steroid, given to attain sufficient blood pressure and urinary output, were quantitatively analyzed during the first 24 hours. OUTCOME MEASURES: Quantity of catecholamines, volume expanders and steroid supplementation as a function of gestational age and childhood outcome at 2 years. RESULTS: Catecholamines and volume loads were increased in a step-wise manner with decreasing gestational age. Intact survival rate was significantly lower in infants born before 25 weeks of gestation compared with the more mature infants. Among infants born at 22 to 24 weeks' gestation, catecholamine and volume load increased significantly in poor outcome infants compared with good outcome infants. CONCLUSIONS: From a developmental viewpoint, progressively larger doses of catecholamine, volume expanders and corticosteroid are required to stabilize circulatory adaptation to neonatal life in infants between 22 to 28 weeks of gestation.

Postmortem data related to drug and toxic substance use in the Federal District, Brazil, from 2006 to 2008.

This study describes the substances involved in fatal events that were investigated by the Forensic Medicine Institute of the Federal District, Brazil, from 2006 to 2008. The presence of pesticides was investigated in liver or stomach content samples by thin-layer chromatography; amphetamines, benzodiazepines, barbiturates, tetra-hydro-cannabinol (THC), cocaine and opioids were analyzed in urine samples by immunoassay. A total of 8736 exams were performed, of which 21.7% tested positive for at least one compound investigated. Men were involved in over 90% of positive cases; most individuals were between the ages of 18 and 30. Alcohol was detected in 47.4% of the blood samples, with over 30% presenting BAC levels higher than 1g/L. Cocaine was present in 21.6%, and THC in 17.5% of the urine samples analyzed. Pesticides were found in 13.3% of the 188 cases investigated, mostly aldicarb, which is the main component of chumbinho, an illegal rodenticide available in the country. Among pharmaceutical drugs, benzodiazepines were the most detected, with 29 samples testing positive (4.6% of the samples analyzed). Most of the individuals who died from traumatism or hypovolemia tested positive for alcohol. Death from intoxication/poisoning corresponded to 1.8% of all positive cases, mainly from the ingestion of pesticides. This is the first Brazilian study reporting data on toxic chemicals from postmortem material. The results confirm other epidemiological data that indicate pesticide as the major cause of fatal poisonings in Brazil.

The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation.

OBJECTIVES: Organ failure worsens outcome in sepsis. The Sequential Organ Failure Assessment (SOFA) score numerically quantifies the number and severity of failed organs. We examined the utility of the SOFA score for assessing outcome of patients with severe sepsis with evidence of hypoperfusion at the time of emergency department (ED) presentation. DESIGN: Prospective observational study. SETTING: Urban, tertiary ED with an annual census of >110,000. PATIENTS: ED patients with severe sepsis with evidence of hypoperfusion. INCLUSION CRITERIA: suspected infection, two or more criteria of systemic inflammation, and either systolic blood pressure <90 mm Hg after a fluid bolus or lactate >or=4 mmol/L. EXCLUSION CRITERIA: age <18 years or need for immediate surgery. INTERVENTIONS: SOFA scores were calculated at ED recognition (T0) and 72 hours after intensive care unit admission (T72). The primary outcome was in-hospital mortality. The area under the receiver operating characteristic curve was used to evaluate the predictive ability of SOFA scores at each time point. The relationship between Delta SOFA (change in SOFA from T0 to T72) was examined for linearity. RESULTS: A total of 248 subjects aged 57 +/- 16 years, 48% men, were enrolled over 2 years. All patients were treated with a standardized quantitative resuscitation protocol; the in-hospital mortality rate was 21%. The mean SOFA score at T0 was 7.1 +/- 3.6 points and at T72 was 7.4 +/- 4.9 points. The area under the receiver operating characteristic curve of SOFA for predicting in-hospital mortality at T0 was 0.75 (95% confidence interval 0.68-0.83) and at T72 was 0.84 (95% confidence interval 0.77-0.90). The Delta SOFA was found to have a positive relationship with in-hospital mortality. CONCLUSIONS: The SOFA score provides potentially valuable prognostic information on in-hospital survival when applied to patients with severe sepsis with evidence of hypoperfusion at the time of ED presentation.

Candesartan improves survival following severe hypovolemia in pigs; a role for the angiotensin II type 2 receptor?

OBJECTIVE: To investigate the involvement of intestinal angiotensin II type 2 receptors in the outcome of acute severe hypovolemia as well as systemic and regional mesenteric hemodynamics and intestinal mucosal functions in anesthetized pigs. DESIGN AND SETTING: Prospective, interventional animal study in a university research laboratory. SUBJECTS: 53 landrace pigs, 28-35 kg. INTERVENTIONS: 30+30% or 20+20% hemorrhage of estimated total blood volume followed by retransfusion performed in untreated controls, in animals treated with the angiotensin II type 1 receptor blocker candesartan or with a combination of candesartan and the angiotensin II type 2 receptor blocker PD123319. MEASUREMENTS AND RESULTS: Following 30+30% hemorrhage the candesartan-treated animals attained a significantly higher survival rate than controls and animals treated with PD123319 in combination with candesartan. Less pronounced hemorrhage (20+20%) resulted in no mortality and functional variables were assessed. A significantly higher output of jejunal intraluminal nitric oxide occurred during hypovolemia in the candesartan treated group than in controls and animals that received PD123319 in combination with candesartan. Jejunal transmucosal potential difference was significantly better preserved after retransfusion in candesartan-treated animals than in controls. Expression of angiotensin II type 2 receptors in intestinal tissue was significantly higher in animals surviving the 30+30% hemorrhage than in nonsurvivors. CONCLUSIONS: Lethal circulatory failure is possibly influenced by use of angiotensin receptor ligands, and activation of intestinal angiotensin II type 2 receptors may play a significant role in improving the outcome of severe hypovolemia.