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Background: Vasopressors are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock.Objectives: The objectives are to review safety and efficacy of vasopressors, pathophysiology, agents that decrease vasopressor dose, predictive biomarkers, β1-blockers, and directions for research.Methods: The quality of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE).Results: Vasopressors bind adrenergic: α1, α2, β1, β2; vasopressin: AVPR1a, AVPR1B, AVPR2; angiotensin II: AG1, AG2; and dopamine: DA1, DA2 receptors inducing vasoconstriction. Vasopressor choice and dose vary because of patients and physician practice. Adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. No randomized controlled trials of vasopressors showed a significant difference in 28-day mortality rate. Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation. Some strategies that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality while corticosteroids have decreased 28-day mortality significantly in some (two large trials) but not all trials. In norepinephrine-refractory patients, vasopressin or epinephrine may be added. A new vasopressor, angiotensin II, may be useful in profoundly hypotensive patients. Dobutamine may be added because vasopressors may decrease ventricular contractility. Dopamine is recommended only in bradycardic patients. There are potent vasopressors with limited evidence (e.g. methylene blue, metaraminol) and novel vasopressors in development (selepressin).Conclusions: Norepinephrine is first choice followed by vasopressin or epinephrine. Angiotensin II and dopamine have limited indications. In future, predictive biomarkers may guide vasopressor selection and novel vasopressors may emerge. [ABSTRACT FROM AUTHOR]

Purpose: Although the definition of septic shock has been standardized, some variation in mortality rates among clinical trials is expected. Insights into the sources of heterogeneity may influence the design and interpretation of septic shock studies. We set out to identify inclusion criteria and baseline characteristics associated with between-trial differences in control group mortality rates.Methods: We conducted a systematic review of RCTs published between 2006 and 2018 that included patients with septic shock. The percentage of variance in control-group mortality attributable to study heterogeneity rather than chance was measured by I2. The association between control-group mortality and population characteristics was estimated using linear mixed models and a recursive partitioning algorithm.Results: Sixty-five septic shock RCTs were included. Overall control-group mortality was 38.6%, with significant heterogeneity (I2 = 93%, P < 0.0001) and a 95% prediction interval of 13.5-71.7%. The mean mortality rate did not differ between trials with different definitions of hypotension, infection or vasopressor or mechanical ventilation inclusion criteria. Population characteristics univariately associated with mortality rates were mean Sequential Organ Failure Assessment score (standardized regression coefficient (β) = 0.57, P = 0.007), mean serum creatinine (β = 0.48, P = 0.007), the proportion of patients on mechanical ventilation (β = 0.61, P < 0.001), and the proportion with vasopressors (β = 0.57, P = 0.002). Combinations of population characteristics selected with a linear model and recursive partitioning explained 41 and 42%, respectively, of the heterogeneity in mortality rates.Conclusions: Among 65 septic shock trials, there was a clinically relevant amount of heterogeneity in control group mortality rates which was explained only partly by differences in inclusion criteria and reported baseline characteristics. [ABSTRACT FROM AUTHOR]

The article offers information regarding permissive hypotension during shock resuscitation. It mentions that targeting a normal blood pressure during resuscitation has been a core element of shock management, but trials are now evaluating the effects of permissive hypotension. It states that chronic hypertension status and information on blood pressure control are unreliable and unavailable during the early phases of resuscitation.

Purpose: In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock.Methods: We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60-65 mmHg) versus a higher (75-80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups.Results: A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95% CI 7-11). In the lower and higher MAP groups, we observed deviations on 12 versus 8% of all days on vasopressors (p = 0.059). Risks of cardiac arrhythmias (20 versus 36%, p = 0.07) and hospital mortality (30 versus 33%, p = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60%, p = 0.03) but not in younger patients.Conclusions: This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy. [ABSTRACT FROM AUTHOR]

The authors comment on the use of serum lactate concentration in guiding physicians in the diagnosis of shock and use of resuscitation strategies. They discuss the definition of shock, lactate formation in shock, sources of blood lactate during shock, and elevated lactate levels in shock as predictor of adverse outcome.

The article discusses about shock resuscitation targeted towards the restoration of parameters such as blood pressure, acid/base indicators, and partial pressures of gases. It also mentions the problems with acquisition of microcirculation data, issues with interpretation of near-infrared spectroscopy (NIRS) and non-invasive handheld video-microscopy (HVM) data, and the framework of early goal-directed therapy (EGDT),.

The article provides information on cytokine release syndrome (CRS), an uncontrolled systemic inflammatory reaction. Topics discussed include epidemiology of CRS, pathophysiology, and importance of early recognition for the effective management of CRS. Strategies to decrease the risk of severe CRS are also mentioned.

Purpose: To assess the feasibility, image quality, diagnostic accuracy, therapeutic impact and tolerance of diagnostic and hemodynamic assessment using a novel miniaturized multiplane transesophageal echocardiography (TEE) probe in ventilated ICU patients with cardiopulmonary compromise.Study Design: Prospective, descriptive, single-center study.Methods: Fifty-seven ventilated patients with acute circulatory or respiratory failure were assessed, using a miniaturized multiplane TEE probe and a standard TEE probe used as reference, randomly by two independent experienced operators. Measurements of hemodynamic parameters were independently performed off-line by a third expert. Diagnostic groups of acute circulatory failure (n = 5) and of acute respiratory failure (n = 3) were distinguished. Hemodynamic monitoring was performed in 9 patients using the miniaturized TEE probe. TEE tolerance and therapeutic impact were reported.Results: The miniaturized TEE probe was easier to insert than the standard TEE probe. Despite lower imaging quality of the miniaturized TEE probe, the two probes had excellent diagnostic agreement in patients with acute circulatory failure (Kappa: 0.95; 95% CI: 0.85-1) and with acute respiratory failure (Kappa: 1; 95% CI: 1.0-1.0). Accordingly, therapeutic strategies derived from both TEE examinations were concordant (Kappa: 0.82; 95% CI: 0.66-0.97). The concordance between quantitative hemodynamic parameters obtained with both TEE probes was also excellent. No relevant complication secondary to TEE probes insertion occurred.Conclusions: Hemodynamic assessment of ventilated ICU patients with cardiopulmonary compromise using a miniaturized multiplane TEE probe appears feasible, well-tolerated, and relevant in terms of diagnostic information and potential therapeutic impact. Further larger-scale studies are needed to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the association between early fluid accumulation and mortality in children with shock states. Methods: We retrospectively reviewed children admitted in shock states to the pediatric intensive care unit (ICU) at a tertiary level children's hospital over a 7-month period. The study was designed as a matched case-control study. Children with early fluid overload, defined as fluid accumulation of ≥10 % of admission body weight during the initial 3 days, were designated as the cases. They were compared with matched controls without early fluid accumulation. Cases and controls were matched for age, severity of illness at ICU admission and need for organ support. They were compared with respect to all-cause ICU mortality and other secondary outcomes. Results: A total of 114 children (age range 0-17.4 years; N = 42 cases and 72 matched controls) met the study criteria. Mortality rate was 13 % (15/114) in this cohort. Multivariable logistic regression analysis identified the presence of early fluid overload [adjusted odds ratio (OR) 9.17, 95 % confidence interval (CI) 2.22-55.57], its severity (adjusted OR 1.11, 95 % CI 1.05-1.19) and its duration (adjusted OR 1.61, 95 % CI 1.21-2.28) as independent predictors of mortality. Cases had higher mortality than the controls (26 vs. 6 %; p 0.003), and this difference remained significant in the matched analysis (37 vs. 3 %; p 0.002). Conclusion: The presence, severity and duration of early fluid are associated with increased ICU mortality in children admitted to the pediatric ICU in shock states. [ABSTRACT FROM AUTHOR]

Purpose: Few data are available about optimal nutrition modalities in mechanically ventilated patients with shock. Our objective was to assess associations linking early nutrition (<48 h after intubation), feeding route and calorie intake to mortality and risk of ventilator-associated pneumonia (VAP) in patients with invasive mechanical ventilation (IMV) and shock. Methods: In the prospective OutcomeRea database, we identified adults with IMV >72 h and shock (arterial systolic pressure <90 mmHg) within 48 h after intubation. A marginal structural Cox model was used to create a pseudo-population in which treatment was unconfounded by subject-specific characteristics. Results: We included 3,032 patients. Early nutrition was associated with lower day-28 mortality [HR 0.89, 95 % confidence interval (CI) 0.81-0.98, P = 0.01] and day-7 mortality (HR 0.76, CI 0.66-0.87, P < 0.001) but not with lower day-7 to day-28 mortality (HR 1.00, CI 0.89-1.12, P = 0.98). Early nutrition increased VAP risk over the 28 days (HR 1.08, CI 1.00-1.17, P = 0.046) and until day 7 (HR 7.17, CI 6.27-8.19, P < 0.001) but decreased VAP risk from days 7 to 28 (HR 0.85, CI 0.78-0.92, P < 0.001). Compared to parenteral feeding, enteral feeding was associated with a slightly increased VAP risk (HR 1.11, CI 1.00-1.22, P = 0.04) but not with mortality. Neither mortality nor VAP risk differed between early calorie intakes of ≥20 and <20 kcal/kg/day. Conclusion: In mechanically ventilated patients with shock, early nutrition was associated with reduced mortality. Neither feeding route nor early calorie intake was associated with mortality. Early nutrition and enteral feeding were associated with increased VAP risk. [ABSTRACT FROM AUTHOR]

Purpose: Skin mottling is frequent and can be associated with an increased mortality rate in ICU patients with septic shock. Its overall incidence in ICU and its impact on outcome is unknown. We aimed to assess the incidence of skin mottling over the knee among all critically ill patients admitted in ICU and its role on their outcome. Methods: An observational study over a 1-year period in a 15-bed medical ICU of a teaching hospital. Skin mottling over the knee was prospectively and qualitatively assessed by trained nurses. Results: Incidence of skin mottling was 29% (230 of 791 patients) in overall, and 49% (32 of 65 patients) in the subset of patients admitted for septic shock. Skin mottling was present on the day on admission in 65% of patients and persisted more than 6 h in 59% of cases. In-ICU mortality was 8% in patients without mottling, 30% in patients with short skin mottling and 40% in patients with persistent skin mottling ( p < 0.01 between all groups). In the overall population, skin mottling over the knee was associated with in-ICU mortality independently from SAPS II (aOR 3.29 [95% CI, 2.08-5.19], p < 0.0001). Among patients with skin mottling over the knee, persistence of skin mottling remained associated with increased in-ICU mortality independently of organ dysfunctions at the mottling onset (OR 2.77 [95% CI, 1.34-5.72], p = 0.004). Conclusions: Skin mottling is frequent in the general population of patients admitted in ICU. Occurrence and persistence of skin mottling are independently associated with in-ICU mortality. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether there was an association between adjunctive therapy with IgM-enriched immunoglobulin (IgM) and the 30-day mortality rate in patients with septic shock. Methods: In 2008 we introduced IgM as a possible adjunctive therapy to be provided within 24 h after shock onset in the management protocol for patients with septic shock. In this retrospective study we included the adult patients suitable for IgM therapy admitted to our ICU from January 2008 to December 2011. An unadjusted comparison between patients who did or did not receive IgM therapy, a multivariate logistic model adjusted for confounders and propensity score-based matching were used to evaluate the association between early IgM treatment and mortality. Results: One hundred and sixty-eight patients were included in the study. Of these, 92 (54.8 %) received IgM therapy. Patients who did or did not receive IgM were similar with regards to infection characteristics, severity scores and sepsis treatment bundle compliance. Patients who received IgM were more likely to have blood cultures before antibiotics and to attain a plateau inspiratory pressure less than 30 cmHO ( p < 0.05). The 30-day mortality rate was reduced by 21.1 % ( p < 0.05) in the group that received IgM compared to the group that did not. The multivariate adjusted regression model (OR 0.17; CI 95 % 0.06-0.49; p = 0.001) and the propensity score-based analysis (OR 0.35; CI 95 % 0.14-0.85; p = 0.021) confirmed that IgM therapy was associated with reduced mortality at 30 days after the onset of septic shock. Conclusions: Our experience indicates that early adjunctive treatment with IgM may be associated with a survival benefit in patients with septic shock. However, additional studies are needed to better evaluate the role of IgM therapy in the early phases of septic shock. [ABSTRACT FROM AUTHOR]

The article presents an update on blood purification in the treatment of sepsis. Topics covered include effect of the treatment of septic shock patients with polymyxin B hemoperfusion, confirmation of endotoxemia by the endotoxin activity assay (EAA), and detrimental effects of the removal of endotoxin/cytokines.

Purpose: We hypothesized that a targeted temperature of 33 °C as compared to that of 36 °C would increase survival and reduce the severity of circulatory shock in patients with shock on admission after out-of-hospital cardiac arrest (OHCA). Methods: The recently published Target Temperature Management trial (TTM-trial) randomized 939 OHCA patients with no difference in outcome between groups and no difference in mortality at the end of the trial in a predefined subgroup of patients with shock at admission. Shock was defined as a systolic blood pressure of <90 mm Hg for >30 min or the need of supportive measures to maintain a blood pressure ≥90 mmHg and/or clinical signs of end-organ hypoperfusion. In this post hoc analysis reported here, we further analyzed the 139 patients with shock at admission; all had been randomized to receive intervention at 33 °C (TTM33; n = 71) or 36 °C (TTM36; n = 68). Primary outcome was 180-day mortality. Secondary outcomes were intensive care unit (ICU) and 30-day mortality, severity of circulatory shock assessed by mean arterial pressure, serum lactate, fluid balance and the extended Sequential Organ Failure assessment (SOFA) score. Results: There was no significance difference between targeted temperature management at 33 °C or 36 °C on 180-day mortality [log-rank test, p = 0.17, hazard ratio 1.33, 95 % confidence interval (CI) 0.88-1.98] or ICU mortality (61 vs. 44 %, p = 0.06; relative risk 1.37, 95 % CI 0.99-1.91). Serum lactate and the extended cardiovascular SOFA score were higher in the TTM33 group ( p < 0.01). Conclusions: We found no benefit in survival or severity of circulatory shock with targeted temperature management at 33 °C as compared to 36 °C in patients with shock on admission after OHCA. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether invasive and non-invasive blood pressure (BP) monitoring allows the identification of patients who have responded to a fluid challenge, i.e., who have increased their cardiac output (CO). Methods: Patients with signs of circulatory failure were prospectively included. Before and after a fluid challenge, CO and the mean of four intra-arterial and oscillometric brachial cuff BP measurements were collected. Fluid responsiveness was defined by an increase in CO ≥10 or ≥15 % in case of regular rhythm or arrhythmia, respectively. Results: In 130 patients, the correlation between a fluid-induced increase in pulse pressure (ΔPP) and fluid-induced increase in CO was weak and was similar for invasive and non-invasive measurements of BP: r² = 0.31 and r² = 0.29, respectively (both p < 0.001). For the identification of responders, invasive ΔPP was associated with an area under the receiver-operating curve (AUC) of 0.82 (0.74-0.88), similar ( p = 0.80) to that of non-invasive ΔPP [AUC of 0.81 (0.73-0.87)]. Outside large gray zones of inconclusive values (5-23 % for invasive ΔPP and 4-35 % for non-invasive ΔPP, involving 35 and 48 % of patients, respectively), the detection of responsiveness or unresponsiveness to fluid was reliable. Cardiac arrhythmia did not impair the performance of invasive or non-invasive ΔPP. Other BP-derived indices did not outperform ΔPP. Conclusions: As evidenced by large gray zones, BP-derived indices poorly reflected fluid responsiveness. However, in our deeply sedated population, a high increase in invasive pulse pressure (>23 %) or even in non-invasive pulse pressure (>35 %) reliably detected a response to fluid. In the absence of a marked increase in pulse pressure (<4-5 %), a response to fluid was unlikely. [ABSTRACT FROM AUTHOR]

Objective: Brain injury is well established as a cause of early mortality after out-of-hospital cardiac arrest (OHCA), but postresuscitation shock also contributes to these deaths. This study aims to describe the respective incidence, risk factors, and relation to mortality of post-cardiac arrest (CA) shock and brain injury. Design: Retrospective analysis of an observational cohort. Setting: 24-bed medical intensive care unit (ICU) in a French university hospital. Patients: All consecutive patients admitted following OHCA were considered for analysis. Post-CA shock was defined as a need for infusion of vasoactive drugs after resuscitation. Death related to brain injury included brain death and care withdrawal for poor neurological evolution. Intervention: None. Measurements and main results: Between 2000 and 2009, 1,152 patients were admitted after OHCA. Post-CA shock occurred in 789 (68 %) patients. Independent factors associated with its onset were high blood lactate and creatinine levels at ICU admission. During the ICU stay, 269 (34.8 %) patients died from post-CA shock and 499 (65.2 %) from neurological injury. Age, raised blood lactate and creatinine values, and time from collapse to restoration of spontaneous circulation increased the risk of ICU mortality from both shock and brain injury, whereas a shockable rhythm was associated with reduced risk of death from these causes. Finally, bystander cardiopulmonary resuscitation (CPR) decreased the risk of death from neurological injury. Conclusions: Brain injury accounts for the majority of deaths, but post-CA shock affects more than two-thirds of OHCA patients. Mortality from post-CA shock and brain injury share similar risk factors, which are related to the quality of the rescue process. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the effects of minor variations in the definition and measurement of systemic inflammatory response syndrome (SIRS) criteria and organ failure on the observed incidences of sepsis, severe sepsis and septic shock. Methods: We conducted a prospective, observational study in a tertiary intensive care unit in The Netherlands between January 2009 and October 2010. A total of 1,072 consecutive adults were included. We determined the upper and lower limits of the measured incidence of sepsis by evaluating the influence of the use of an automated versus a manual method of data collection, and variations in the number of SIRS criteria, concurrency of SIRS criteria, and duration of abnormal values required to make a particular diagnosis. Results: The measured incidence of SIRS varied from 49 % (most restrictive setting) to 99 % (most liberal setting). Subsequently, the incidences of sepsis, severe sepsis and septic shock ranged from 22 to 31 %, from 6 to 27 % and from 4 to 9 % for the most restrictive versus the most liberal measurement settings, respectively. In non-infected patients, 39-98 % of patients had SIRS, whereas still 17-6 % of patients without SIRS had an infection. Conclusions: The apparent incidence of sepsis heavily depends on minor variations in the definition of SIRS and mode of data recording. As a consequence, the current consensus criteria do not ensure uniform recruitment of patients into sepsis trials. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prognostic information of chromogranin A (CgA), a marker associated with adrenergic tone and myocardial function, in patients with severe sepsis. Methods: CgA levels were measured at the time of study inclusion and 72 h later in 232 patients with severe sepsis recruited from 24 ICUs in Finland (FINNSEPSIS study). Results: Sixty-five patients (28 %) died during the index hospitalization. CgA levels at inclusion and after 72 h correlated with several established indices of risk in sepsis. Patients who died during the hospitalization had higher baseline CgA levels than hospital survivors: 14.0 (Q1-3, 7.4-27.4) versus 9.1 (5.9-15.8) nmol/l, P = 0.002, and after 72 h: 16.2 (9.0-31.1) versus 9.8 (6.0-18.0) nmol/l, P = 0.001. Prior cardiovascular disease ( P = 0.04) and cardiovascular SOFA levels on day 3 ( P = 0.03) were associated with higher CgA levels after 72 h by linear regression. CgA levels on study inclusion and after 72 h were independently associated with hospital mortality by logistic regression: OR (logarithmically transformed CgA levels) 1.95 (95 % CI 1.01-3.77), P = 0.046 and OR 2.03 (95 % CI 1.18-3.49), P = 0.01, respectively. The prognostic accuracy was comparable for CgA measurements and SAPS II score, and the addition of CgA measurements to the SAPS II score improved risk stratification of the patients as assessed by the category-free net reclassification index. A CgA level >6.6 nmol/l on study inclusion was associated with septic shock during the hospitalization. Conclusion: CgA levels measured during hospitalization for severe sepsis are associated with cardiovascular dysfunction and may provide additional prognostic information in patients with severe sepsis. [ABSTRACT FROM AUTHOR]

Purpose: To document the relationship between stroke volume (SV) and pulse pressure (PP) recorded at the femoral and aortic sites during volume expansion (VE) in patients in shock. We hypothesized that non-invasively estimated aortic PP would exhibit the same ability as PP recorded invasively at the femoral level to track SV changes. Methods: Included in this prospective study were 56 ICU patients needing VE. Femoral PP (indwelling catheter), aortic PP (tonometry) and cardiac output (thermodilution) were recorded before and after VE. Responders were defined as patients who showed an increase in SV of ≥15% after VE. Results: Of the 56 included patients in shock, 39 (age 57 ± 14 years, SAPS II 46 ± 18) completed the study. At both sites, PP increased after VE in responders ( n = 17, mean SV increase 30 ± 15%) but not in non-responders. In the overall population, there was a positive relationship between VE-induced changes in SV and in PP at the femoral ( r = 0.60, p < 0.001) and aortic ( r = 0.52, p < 0.001) sites. Increases in femoral PP of ≥9% indicated SV increases of ≥15% with 82% sensitivity and 95% specificity. Increases in aortic PP of ≥4.5% indicated SV increases of ≥15% with 76% sensitivity and 82% specificity. Areas under the ROC curves indicated that aortic PP was not different from femoral PP for tracking changes in SV. Conclusion: The ability of non-invasively estimated aortic PP to track fluid response was the same as that of invasively recorded femoral PP. This may have implications for non-invasive haemodynamic monitoring. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include the effects of a fluid challenge on regional tissue perfusion in intensive care unit (ICU) patients, dopamine and norepinephrine for the treatment of shock and the failure of nitroglycerin to recruit the microcirculation of the intestinal villi in ship endotoxemia.

The authors comment on studies on the use of lactate clearance to guide resuscitation in septic shock patients. The studies discussed include one on impaired clearance as a cause of mild hyperlactatemia in stable septic patients, a biphasic curve followed by the time course of lactate normalization during resuscitation, and lastly on limiting fluid resuscitation in patients with a persistent clinical problem but with normal peripheral perfusion.

To determine the effects of passive leg raising (PLR) on hemodynamics and on cardiac function according to the preload dependency defined by the superior vena cava collapsibility index (ΔSVC). Forty patients with shock, sedated and mechanically ventilated, were included. Transesophageal echocardiography was performed. At baseline (T1), two groups were defined according to ΔSVC. Eighteen patients presenting a ΔSVC > 36%, an indicator of preload dependency, formed group 1, whereas 22 patients (group 2) exhibited a ΔSVC < 30% (not preload-dependent). Measurements were then performed during PLR (T2), back to baseline (T3), and after volume expansion (T4) in group 1 only. At T1, ΔSVC was significantly higher in group 1 than in group 2, 50 ± 9% and 7 ± 6%, respectively. In group 1, we found a decrease in ΔSVC at T2 (24 ± 9%) and T4 (17 ± 7%), associated with increased systolic, diastolic and arterial pulse pressures. Cardiac index also increased, from 1.92 ± 0.74 (T1) to 2.35 ± 0.92 (T2) and 2.85 ± 1.2 l/min/m2 (T4) and left ventricular end-diastolic volume from 51 ± 41 to 61 ± 51 and 73 ± 51 ml/m2. None of these variations was found in group 2. No change in heart rate was observed. Hemodynamic changes related to PLR were only induced by increased cardiac preload. [ABSTRACT FROM AUTHOR]

To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C );... [ABSTRACT FROM AUTHOR]

Background: Understanding of sepsis-induced brain dysfunction remains poor, and relies mainly on data from animals or post-mortem studies in patients. The current study provided findings from magnetic resonance imaging of the brain in septic shock.Methods: Nine patients with septic shock and brain dysfunction [7 women, median age 63 years (interquartile range 61-79 years), SAPS II: 48 (44-56), SOFA: 8 (6-10)] underwent brain magnetic resonance imaging including gradient echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), T2-weighted and diffusion isotropic images, and mapping of apparent diffusion coefficient.Results: Brain imaging was normal in two patients, showed multiple ischaemic strokes in two patients, and in the remaining patients showed white matter lesions at the level of the centrum semiovale, predominating around Virchow-Robin spaces, ranging from small multiple areas to diffuse lesions, and characterised by hyperintensity on FLAIR images. The main lesions were also characterised by reduced signal on diffusion isotropic images and increased apparent diffusion coefficient. The lesions of the white matter worsened with increasing duration of shock and were correlated with Glasgow Outcome Score.Conclusion: This preliminary study showed that sepsis-induced brain lesions can be documented by magnetic resonance imaging. These lesions predominated in the white matter, suggesting increased blood-brain barrier permeability, and were associated with poor outcome. [ABSTRACT FROM AUTHOR]

Objective: Shock is a severe syndrome resulting in multiple organ dysfunction and a high mortality rate. The goal of this consensus statement is to provide recommendations regarding the monitoring and management of the critically ill patient with shock.Methods: An international consensus conference was held in April 2006 to develop recommendations for hemodynamic monitoring and implications for management of patients with shock. Evidence-based recommendations were developed, after conferring with experts and reviewing the pertinent literature, by a jury of 11 persons representing five critical care societies.Data Synthesis: A total of 17 recommendations were developed to provide guidance to intensive care physicians monitoring and caring for the patient with shock. Topics addressed were as follows: (1) What are the epidemiologic and pathophysiologic features of shock in the ICU? (2) Should we monitor preload and fluid responsiveness in shock? (3) How and when should we monitor stroke volume or cardiac output in shock? (4) What markers of the regional and micro-circulation can be monitored, and how can cellular function be assessed in shock? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock? One of the most important recommendations was that hypotension is not required to define shock, and as a result, importance is assigned to the presence of inadequate tissue perfusion on physical examination. Given the current evidence, the only bio-marker recommended for diagnosis or staging of shock is blood lactate. The jury also recommended against the routine use of (1) the pulmonary artery catheter in shock and (2) static preload measurements used alone to predict fluid responsiveness.Conclusions: This consensus statement provides 17 different recommendations pertaining to the monitoring and caring of patients with shock. There were some important questions that could not be fully addressed using an evidence-based approach, and areas needing further research were identified. [ABSTRACT FROM AUTHOR]

A 70-year-old male known for hepatitis-B liver cirrhosis and hepatocellular carcinoma, on transplant list, was referred to our ICU team following a microwave ablation of a segment VIII hepatic lesion. Despite angiography and dilation of the IVC and hepatic veins, the liver and kidney functions worsened and the patient needed urgent liver transplantation on the following day. RA right atrium, IVC inferior vena cava Liver thermoablation can rarely cause severe shock consecutive to acute IVC stenosis. [Extracted from the article]

The article comments on the importance of resuscitation to reduce the deaths of infants and children from diarrhea, malaria and bacterial sepsis. The priorities for realizable child survival are: improved access to facilities capable of time-sensitive intravenous fluid resuscitation and determination of fluid composition which can best attain resuscitation goals.

Objective: To develop a clinical practice guideline that provides recommendations for the fluid, i.e. colloid or crystalloid, used for resuscitation in critically ill neonates and children up to the age of 18 years with hypovolemia.Methods: The guideline was developed through a comprehensive search and analysis of the pediatric literature. Recommendations were formulated by a national multidisciplinary committee involving all stakeholders in neonatal and pediatric intensive care and were based on research evidence from the literature and, in areas where the evidence was insufficient or lacking, on consensus after discussions in the committee.Results: Because of the lack of evidence in neonates and children, trials conducted in adults were considered. We found several recent meta-analyses that show excess mortality in albumin-treated groups, compared with crystalloid-treated groups, and one recent large randomized controlled trial that found evidence of no mortality difference. We found no evidence that synthetic colloids are superior to crystalloid solutions.Conclusions: Given the state of the evidence and taking all other considerations into account, the guideline-developing group and the multidisciplinary committee recommend that in neonates and children with hypovolemia the first-choice fluid for resuscitation should be isotonic saline. [ABSTRACT FROM AUTHOR]

Objective: In critical illness, liver dysfunction (LD) is associated with a poor outcome independently of other organ dysfunctions. Since strategies to support liver function are not available, a timely and accurate identification of factors promoting LD may lead to prevention or attenuation of its consequences. The aim of this study was to assess risk factors for LD in critically ill patients.Design: Prospective, observational study.Setting: A multidisciplinary intensive care unit (ICU) of a university hospital.Patients: All patients consecutively admitted over a 6-month period.Intervention: None.Measurements and Results: LD was defined as serum bilirubin levels >or=2 mg/dl and lasting for at least 48 h. Out of 283 patients, 141 matched inclusion criteria. Forty-four patients (31.2%) showed LD (LD group), while 97 (68.8%) were included in control group (C group). A binomial analysis showed that LD occurrence was associated with moderate (odds ratio [OR] 3.11; p=0.04) and severe shock (OR 3.46; p= 0.05), sepsis (OR 3.03; p=0.04), PEEP ventilation (OR 4.25; p=0.006), major surgery (OR 4.03; p=0.03), and gram-negative infections (OR 3.94; p=0.002). In stepwise multivariate analysis, the single independent predictive factors of LD resulted in severe shock (p=0.002), sepsis (p=0.03), PEEP ventilation (p=0.04), and major surgery (p=0.05).Conclusions: In critically ill patients jaundice is common, and severe shock states, sepsis, mechanical ventilation with PEEP and major surgery are critical risk factors for its onset. Since there is no specific treatment, prompt resuscitation, treatment of sepsis and meticulous supportive care will likely reduce its incidence and severity. [ABSTRACT FROM AUTHOR]

Objective: Esophageal Doppler allows continuous monitoring of stroke volume index (SVI) and corrected flow time (FTc). We hypothesized that variations in stroke output index SOI (SVI/FTc) during volume expansion can predict the hemodynamic response to subsequent fluid loading better than the static values.Design and Setting: Prospective study in the intensive care unit of a university hospital.Patients: Fifty-one patients with circulatory failure were monitored by esophageal Doppler.Interventions: Patients who responded to a first fluid challenge received a second one. Patients who responded to both were classified as responders-responders, and those who did not respond to the second as responders-nonresponders. In these two groups we compared DeltaSVI, DeltaFTc, and DeltaSOI during each fluid challenge and also static values at the end of each fluid challenge.Measurements and Results: After the first fluid challenge DeltaSOI and DeltaSVI were significantly higher in patients who responded to subsequent volume expansion than in patients who no longer responded. ROC curves showed that DeltaSOI was a better predictor of fluid responsiveness than DeltaSVI. During volume expansion a DeltaSOI value of 11% discriminated between responders and nonresponders to subsequent volume expansion with a sensitivity of 91% and a specificity of 97%. There was no significant difference between the two groups for FTc value at the end of first fluid challenge.Conclusions: Analysis of DeltaSOI during fluid challenge predicts response to subsequent fluid challenge and FTc is not a reliable indicator of cardiac preload. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of fenofibrate, an activator of peroxysome proliferator activated receptor (PPAR) alpha, on vascular endothelium and on hemostasis in a rabbit endotoxic shock model.Design and Setting: Prospective laboratory study in a university laboratory.Subjects: 36 male New Zealand rabbits weighing 2.5-3 kg.Interventions: We determined in vitro vascular reactivity, endothelium CD31-platelet/endothelial cell adhesion molecule (PECAM) 1 immunohistochemistry, plasma coagulation factors, and monocyte tissue factor expression 5 days after onset of endotoxic shock (0.5 mg/kg intravenous bolus, Escherichia coli lipopolysaccharide) with or without treatment by fenofibrate (mixed in the chow at a concentration of 0.5%) for 15 days before lipopolysaccharide injection and 5 days afterward.Measurements and Results: Metabolic acidosis and coagulation activation confirmed presence of shock. Fenofibrate decreased monocyte tissue factor expression. It improved endothelial-dependent relaxation at 5 days (Emax=68.2+/-3.3%, vs. 44.2+/-2.5% in the non-treated group). Endotoxin-induced deendothelialization was significantly decreased by fenofibrate at 5 days (8.5+/-1.3% vs. 19.2+/-3.1% in the nontreated group) .Conclusions: These data indicate for the first time that fenofibrate, an activator of PPAR-alpha, inhibits monocyte tissue factor expression and protects against endothelial dysfunction and histological injury in endotoxin-induced shock. [ABSTRACT FROM AUTHOR]

The strength of the rationale for incorporating total body oxygen consumption (VO(2)) and delivery (DO(2)) into our decision making strategies contrasts with the absence of demonstrated benefits of bedside calculations in clinical practice. This situation mandates a careful reappraisal of the theoretical limitations of bedside calculations of DO(2) and VO(2), including a re-evaluation of the clinical situations in which these calculations are valid. Three levels of complexity can be distinguished when analysing a patient's hemodynamic status: 1) simple cases where investigations can be limited to clinical monitoring, including lactate changes over time; 2) intermediate situations requiring invasive investigations in which continuous monitoring of VO(2)-related variables such as cardiac output and mixed venous oxygen saturation often provide enough information to guide clinical decision; and 3) complex situations where assessment of VO(2) and VO(2)/DO(2) analysis might be recommended. Although studies that support such recommendations are limited they are based on a widely accepted physiological model. VO(2) and DO(2) analysis is also limited by theoretical and technical difficulties. In this article, we discuss the validity of these limitations in the bedside assessment of VO(2) and DO(2), and review data supporting the use of VO(2)/DO(2) analysis in the clinical evaluation of complex cases. [ABSTRACT FROM AUTHOR]

Discusses topics and issues related to oxygen transport in the body. Consumption of energy in during cellular activities in the form of oxygen; Acquisition of oxygen from the degradation of adenosine triphosphate and other high-energy compounds; Concept of oxygen delivery; Relationship between oxygen consumption and oxygen delivery.

Objective: This prospective observational study was undertaken in order to assess pain experienced by intensive care unit patients at the time of extubation and to identify factors associated with pain of at least moderate intensity.Design: Prospective observational study.Setting: Intensive care unit at a university hospital.Patients: During a 1-year period the presence, severity and clinical predictors of orofacial and/or chest pain among patients undergoing removal of endotracheal tubes was assessed.Measurements and Results: Pain was evaluated using a visual analogue scale (VAS). Of 332 extubated patients, 203 could be evaluated. During the peri-extubation period, pain was significantly associated with a SAPS II score more than 36 ( p=0.03) and duration of mechanical ventilation (MV) of 6 days or more ( p=0.002), whereas intubation in the operating room was associated with less pain ( p=0.001). Pain of at least moderate intensity (VAS score >30 mm) was reported by 73% of patients and pain of severe intensity (VAS score >50 mm) was reported by 45% of patients. MV duration of 6 days or more was the only independent risk factor for pain of at least moderate intensity (OR 2.4, 95% CI 1.03-5.4, p=0.04). We also observed that pain had resolved 1 h after extubation in the majority of patients.Conclusion: Our results suggest that, in intensive care unit patients, peri-extubation pain is frequent and should be considered for treatment, especially in patients with longer intubation. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to perform a descriptive approach of the current use of catecholamines by French physicians.Design: A questionnaire of 12 questions with 4 items established by a group of French intensivists.Population: French physicians from 433 departments working in the following practicing areas: intensive care unit (ICU), emergency department, and pre-hospital setting.Measurements: Responding physicians were asked about the catecholamine that they would select in various clinical settings.Results: The response rate was 82%. Of the responding physicians, 277 (78%) worked in an ICU, 28 (8%) in an emergency department, and 21 (6%) in a pre-hospital setting. Dobutamine was chosen for patients with cardiogenic shock by 90% of the respondents. Norepinephrine was the first choice agent as vasopressor in patients with septic shock in 52% of the cases. Dopamine was selected in a clinical setting requiring an optimization of regional blood flow, as in the concept of high-risk surgical patients. Dopexamine was used as a second or third choice agent to improve regional blood flow and cardiac output. The indications of epinephrine for anaphylactic shock and cardio-circulatory arrest were obvious for more than 90% of responding physicians.Conclusion: A lack of standardization appears in the use of catecholamines by French physicians, particularly for improvement of regional circulation and management of high-risk surgical patients. Guidelines that define the place of each catecholamine in these settings are required to improve the quality of prescription. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effects of an intravenous bolus dose of a vasopressin analogue, terlipressin (1 mg), on systemic haemodynamic parameters and gastric mucosal perfusion (GMP) in patients with catecholamine-treated septic shock using a gastric tonometry and laser-Doppler flowmetry technique.Design: Prospective open label study.Settings: Two multidisciplinary intensive care units.Patients: Fifteen patients with norepinephrine-treated septic shock.Interventions: Every patient with mean arterial pressure between 50 and 55 mmHg treated with high dose norepinephrine received an intravenous bolus dose of terlipressin as last resort therapy. A laser-Doppler probe and tonometer were introduced into the gastric lumen.Measurements and Main Results: Terlipressin produced a decrease in cardiac output ( p<0.05), a progressive increase in mean arterial pressure ( p<0.05) and in GMP, detected by laser-Doppler flowmetry ( p<0.05) over 30 min and sustained for at least 24 h. The ratio of GMP to systemic oxygen delivery increased after terlipressin bolus dose ( p<0.05). The gradient between gastric mucosal and arterial PCO(2) tended to be lower after terlipressin, and the difference was statistically significant ( p<0.05) after 8 h. Terlipressin administration significantly increased ( p<0.05) urine output compared to baseline and higher values were found at each set of measurement. The terlipressin-induced increase in urine output was associated with a significantly increased creatinine clearance ( p<0.05). Reduction of the high-dose norepinephrine was observed in all patients ( p<0.05).Conclusions: Our findings showed that, in patients with norepinephrine-treated septic shock, terlipressin increased GMP, urine output and creatinine clearance by an increase in mean arterial pressure. [ABSTRACT FROM AUTHOR]

Objective: To determine the threshold of age that best discriminates the survival of mechanically ventilated patients and to estimate the outcome of mechanically ventilated older patients.Design: International prospective cohort study.Setting: Three hundred sixty-one intensive care units from 20 countries. PATIENTS AND PARTICIPANTS. Five thousand one hundred eighty-three patients mechanically ventilated for more than 12 h.Interventions: None.Measurements and Results: Recursive partitioning and logistic regression were used and an outcome model was derived and validated using independent subgroups of the cohort. Two age thresholds (43 and 70 years) were found, by partitioning recursive analysis, to be associated with outcome. This study focuses on the analysis of patients older than 43 years of age, divided in two subgroups: between 43 and 70 years (middle age group) and older than 70 years (elderly group). Survival in hospital was 45% (95% C.I.: 43-48) for the elderly group and 55% (53-57) for the middle age group ( p<0.001). Advanced age was not associated with prolongation of mechanical ventilation, weaning or length of stay in the ICU and in hospital ( p>0.05). Variables associated with mortality in the elderly were: acute renal failure, shock, Simplified Acute Physiology Score II and a ratio of PaO(2) to FIO(2) more than 150.Conclusions: Older mechanically ventilated patients (age >70 years) had a lower ICU and hospital survival, but the duration of mechanical ventilation, ICU and hospital stay were similar to younger patients. Factors associated with the highest risk of mortality in patients older than 70 were the development of complications during the course of mechanical ventilation, such as acute renal failure and shock. [ABSTRACT FROM AUTHOR]

Objective: To examine the hypothesis that neutrophil chemotaxis to interleukin-8 (IL-8) is reduced in septic shock. Surface expression of neutrophil CXC chemokine receptors and the adhesion molecule CD11b were also examined and associations between disease severity, gas exchange and receptor expression were studied.Design: Prospective cohort clinical study. SETTING. Intensive care unit in a tertiary referral teaching hospital.Patients: Patients with septic shock ( n=15) and healthy controls ( n=8) were studied.Measurements and Results: Daily (for 5 consecutive days) flow cytometric measurements of chemokine and beta integrin surface expression. "In vitro" neutrophil chemotaxis to IL-8 was also compared between patients with sepsis and healthy controls. CXCR2 expression significantly fell, CD11b expression increased and CXCR1 expression was unchanged throughout the study in the septic group compared with healthy controls. CD11b positively correlated with increasing APACHE II scores ( p<0.0001) and worsening PaO(2)/FIO(2) ratios ( p<0.0001). CXCR2 expression negatively correlated with both APACHE II scores ( p=0.016) and PaO(2)/FIO(2) ratios ( p=0.01). There was no correlation between CXCR1 expression and either APACHE II score or PaO(2)/FIO(2) ratios. Chemotaxis to IL-8 was reduced in patients with sepsis compared with healthy volunteers.Conclusions: Surface expression of the chemokine receptor CXCR2 and the beta-integrin CD11b, but not CXCR1, were reduced on neutrophils isolated from patients with septic shock compared with healthy controls. Chemotaxis to IL-8 was also reduced in neutrophils from septic patients compared with healthy controls. The changes in receptor expression correlated with measures of disease severity. [ABSTRACT FROM AUTHOR]

The article presents information on the use of antioxidant therapy in sepsis. there is growing evidence that oxygen derived free radicals are implicated as relevant mediators in sepsis and septic shock. In the past, numerous attempts have yielded discouraging results in the pharmacological treatment of sepsis-related oxidative stress and its sequelae. However, one must not forget that many of these studies have shed light on the complex interplay and pathophysiology of this entity. In this way, the report of researchers C. Ritter and others essentially contributes to a more sophisticated insight into the kinetics of ROS production and the related regulation of enzymatic antioxidant systems. The identification of patients to be treated may be facilitated by knowledge of the early markers of sepsis lethality, and a rationale for preferring a distinct therapeutic approach may therefore be provided.

Objective: Interest has recently focused on the use of neurohormonal markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) as indices of left ventricular systolic dysfunction and prognosis in heart failure. Also, peptides belonging to the interleukin-6 (IL-6) family have been shown to induce ANP and BNP secretion. We hypothesized that BNP and ANP spillover in the peripheral circulation reflects left ventricular dysfunction and IL-6 production in septic shock.Design and Setting: Retrospective, clinical study in the medical intensive care unit of a university hospital.Patients and Participants: 17 patients with septic shock and 19 control subjects.Interventions: Collection of clinical and demographic data in relation to ANP, BNP, IL-6, and soluble TNF receptors (sTNF-R-p55, sTNF-R-p75) in plasma over a period of 4 days.Measurements and Results: In septic shock we found a significant increase in ANP (82.7+/-9.9 vs. 14.9+/-1.2 pg/ml) and BNP (12.4+/-3.6 vs. 5.5+/-0.7 pg/ml). Plasma ANP peaked together with IL-6. Peaks of ANP and IL-6 were significantly correlated (r=0.73; p<0.01). BNP was inversely correlated to cardiac index (r=-0.56; p<0.05).Conclusions: ANP and BNP increase significantly in patients with septic shock. BNP reflects left ventricular dysfunction. ANP is related to IL-6 production rather than to cardiovascular dysfunction. [ABSTRACT FROM AUTHOR]

Male gender predisposes to severe sepsis and septic shock. This effect has been ascribed to higher levels of testosterone. The ESPNIC ARDS database was searched, to determine if there was evidence of a similar male preponderance in severe sepsis in prepubertal patients in spite of low levels of male sex hormones at this age. A total of 72 patients beyond neonatal age up to 8 years of age with sepsis were identified. The male/female (M/F) ratio was 1.7 (1.0;2.7) and differed significantly from non-septic ARDS patients in this age group [n = 209; M/F = 1.0 (0.8;1.3)]. The highest M/F-ratio was observed in the first year of life. The gender-ratio was the same as reported in adult patients with sepsis. In infants between 1 month and 12 months of age, the ratio was 2.8 (1.2;6.1) (Chi2= 5.6; P< 0.01), in children from 1 year to 8 years of age it was 1.2 (0.7;2.2) (n.s.). In a subgroup of patients with severe sepsis or septic shock, caused by other bacteria than Neisseria meningitidis, the M/F-ratio was 2.1 (1.2;3.6) (Chi2= 4.9; P<0.05), while in patients with meningococcal sepsis (n=20) the M/F-ratio was 1.0 (0.4;2.3). In prepubertal ARDS patients with sepsis an increased frequency of male patients is found, comparable to adults. No male preponderance exists in patients with ARDS due to meningococcal septic shock. Since levels of testosterone and other sex hormones are extremely low at this age, we conclude that factors others than testosterone are involved in the male preponderance in severe sepsis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of hypertonic (3%) saline in heatstroke rats with circulatory shock, intracranial hypertension, and cerebral ischemia.Design and Setting: Urethane-anesthetized rats were exposed to a high ambient temperature of 42 degrees C until mean arterial pressure and local cerebral blood flow (CBF) in the corpus striatum began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 24 degrees C.Measurements and Results: Extracellular concentrations of glutamate and lactate/pyruvate ratio (cellular ischemia markers), and glycerol (a cellular injury marker) in the corpus striatum of rat brain were assessed by intracerebral microdialysis methods. Striatal PO(2), temperature, and local CBF were measured with a combined OxyLite PO(2), thermocouple, and OxyFlo LDF, respectively. The values of mean arterial pressure, cerebral perfusion pressure, and striatal CBF and PO(2) in rats treated with 0.9% NaCl solution after the onset of heatstroke were all significantly lower than those in normothermic controls. In contrast, the values of intracranial pressure, brain temperature, and extracellular concentrations of glutamate, glycerol, and lactate/pyruvate in the corpus striatum were greater. Intravenous infusion of hypertonic (3%) saline solution either "0" time before the start of heat exposure or right after the onset of heatstroke significantly attenuated the heatstroke-induced arterial hypotension, intracranial hypertension, decreased cerebral perfusion, and cerebral ischemia and damage and resulted in prolongation of survival time.Conclusions: Our results strongly suggest that the experimental heatstroke syndromes can be effectively prevented and treated by hypertonic saline. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of changing the amount of pre-dilution replacement fluid on the sieving coefficient (SC) and mass transfer of small solutes during isovolaemic high-volume haemofiltration (HVHF).Design and Setting: Prospective interventional study in the intensive care unit of a tertiary university hospital.Patients: Eight patients with septic shock.Interventions: Isovolaemic HVHF (6 l/h of replacement fluid) was performed. The proportion of replacement fluid delivered in pre-filter was altered to progressively decrease it from 6 to 0 l/h. Samples were simultaneously taken from the "pre-filter", "post-filter" and ultrafiltrate (UF) sampling ports.Measurements and Results: Sodium, potassium, chloride, total calcium, total magnesium, phosphate, total CO(2), urea, creatinine and glucose concentrations were measured in each sample. The sieving coefficients of chloride, total CO(2), phosphate, urea and glucose were higher than 1 in most pre-dilution states. The sieving coefficients of sodium, potassium, calcium, magnesium, total CO(2) and urea decreased significantly with decreasing pre-dilution fluid rate. The sieving coefficients of chloride and glucose increased with decreasing pre-dilution fluid rate. There was a significant mass gain of sodium and glucose under all pre-dilution conditions. Mass chloride gains decreased with decreasing pre-dilution rates and changed into chloride loss during 6 l/h of post-dilution. Decreasing pre-dilution improved urea and creatinine mass removal.Conclusions: Small solute SC and mass transfer during isovolaemic HVHF are significantly affected by the proportion of replacement fluid administered pre-filter. Isovolaemic HVHF is neither isonatraemic nor isochloraemic. [ABSTRACT FROM AUTHOR]

Objective: To audit paediatric intensive care unit (PICU) transfer activity and transfer-related adverse events in a resource-limited setting.Design and Setting: Twenty-two bed regional PICU of a university children's hospital in Cape Town, South Africa. Prospective 1-year audit of all children transferred directly from other hospitals. Data were collected for patient demographics, diagnostic category, referring hospital, transferring personnel, mode of transport, and technical, clinical, and critical adverse events. Data are median (interquartile range) or percentages. The transfers of 202 children, median age 2.8 months (1.1-14), median weight 3.5 kg (2.5-8.1) were analysed.Results: Most transfers were performed by paramedic personnel (82%) and via road ambulance (76%). One or more technical adverse events occurred in 36%, clinical adverse events in 27%, and critical adverse events in 9% of children. Retrievals by intensive care staff (10%), all from rural hospitals, had a lower incidence of technical adverse events (0%). Children transferred from non-academic hospitals within the metropolitan area had the highest incidence of technical (44%), clinical (39%), and critical (17%) adverse events. Crude mortality was 17% ( n=34). Technical adverse events were not associated with mortality. Non-survivors were more likely to develop shock (32%) or hypoxia (26%) during transfer than survivors (10% and 11%, respectively).Conclusions: There is a high incidence of transfer-related adverse events, most commonly in transfers from non-academic metropolitan hospitals. Further studies are needed to assess the impact of regional paediatric life support training or a specialised retrieval team on clinical adverse events and mortality. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of high-volume hemofiltration (HVHF) with lactate-buffered replacement fluids on acid-base balance.Design: Randomized crossover study.Setting: Intensive Care Unit of Tertiary Medical CenterParticipants: Ten patients with septic shock and acute renal failure.Interventions: Random allocation to 8 h of isovolemic high-volume hemofiltration (ultrafiltration rate: 6 l/h) or 8 h of isovolemic continuous venovenous hemofiltration (ultrafiltration rate: 1 l/h) with lactate-buffered replacement fluid with subsequent crossover.Measurements and Results: We measured blood gases, electrolytes, albumin, and lactate concentrations and completed quantitative biophysical analysis of acid-base balance changes. Before high-volume hemofiltration, patients had a slight metabolic alkalosis [pH: 7.42; base excess (BE) 2.4 mEq/l] despite hyperlactatemia (lactate: 2.51 mmol/l). After 2 h of high-volume hemofiltration, the mean lactate concentration increased to 7.30 mmol/l ( p=0.0001). However, a decrease in chloride, strong ion difference effective, and strong ion gap (SIG) compensated for the effect of iatrogenic hyperlactatemia so that the pH only decreased to 7.39 ( p=0.05) and the BE to -0.15 ( p=0.001). After 6 h, despite persistent hyperlactatemia (7 mmol/l), the pH had returned to 7.42 and the BE to 2.45 mEq/l. These changes remained essentially stable at 8 h. Similar but less intense changes occurred during continuous venovenous hemofiltration.Conclusions: HVHF with lactate-buffered replacement fluids induces iatrogenic hyperlactatemia. However, such hyperlactatemia only has a mild and transient acidifying effect. A decrease in chloride and strong ion difference effective and the removal of unmeasured anions all rapidly compensate for this effect. [ABSTRACT FROM AUTHOR]

Hypothesis: Mortality in children with shock is more closely related to the nature, rather than the magnitude (base deficit/excess), of a metabolic acidosis.Objective: To examine the relationship between base excess (BE), hyperlactataemia, hyperchloraemia, 'unmeasured' strong anions, and mortality.Design: Prospective observational study set in a multi-disciplinary Paediatric Intensive Care Unit (PICU).Patients: Forty-six children, median age 6 months (1.5-14.4), median weight 5 kg (3.2-8.8), admitted to PICU with shock.Interventions: Predicted mortality was calculated from the paediatric index of mortality (PIM) score. The pH, base excess, serum lactate, corrected chloride, and 'unmeasured' strong anions (Strong Ion Gap) were measured or calculated at admission and 24 h.Measurements and Results: Observed mortality ( n=16) was 35%, with a standardised mortality ratio (SMR) of 1.03 (95% CI 0.71-1.35). There was no significant difference in admission pH or BE between survivors and nonsurvivors. There was no association between elevation of 'unmeasured' anions and mortality, although there was a trend towards hyperchloraemia in survivors ( P=0.08). Admission lactate was higher in nonsurvivors (median 11.6 vs 3.3 mmol/l; P=0.0003). Area under the mortality receiver operating characteristic curve for lactate was 0.83 (955 CI 0.70-0.95), compared to 0.71 (95% CI 0.53-0.88) for the PIM score. Admission lactate level >5 mmol/l had maximum diagnostic efficiency for mortality, with a likelihood ratio of 2.0.Conclusion: There is no association between the magnitude of metabolic acidosis, quantified by the base excess, and mortality in children with shock. Hyperlactataemia, but not elevation of 'unmeasured' anions, is predictive of a poor outcome. [ABSTRACT FROM AUTHOR]

Discusses the findings that pathologic state of shock is characterized by profound changes in tissue perfusion and metabolism. Identification of the hierarchy of priority among the various organs; Concepts about the use of adrenergic agents depending on the specific adrenoceptor profile of either endogenous and synthetic catecholamines; Effects of the treatment on regional blood flow and metabolism.

Evaluates the effects of hypoperfusion on the increase of mortality. Analysis of the outcomes in pulmonary embolism; Assessment on the result of the combination of embolus size and cardiopulmonary status; Effects of the potential mortality benefits on the hemorrhagic risks.

Objectives: To define the role of procalcitonin in the differential diagnosis, prognosis and follow-up of critically ill patients.Design: Prospective study during the 2-year period from January 1998-2000.Patients: One hundred nineteen critically ill patients: 29 with systemic inflammatory response syndrome (SIRS) without any signs of infection, 11 with sepsis, 17 with severe sepsis, 10 with septic shock and 52 controls. Daily measurements of procalcitonin were performed by an immunocheminoluminometric assay, and values were correlated to the clinical characteristics of the patients.Results: Mean concentrations of procalcitonin were 5.45 (95% CI: 2.11, 8.81), 7.29 (95% CI: -1.92,14.59), 6.26 (95% CI: -1.32, 13.85) and 38.76 ng/ml (95% CI: 0.15, 77.38) on the 1st day in patients with SIRS, sepsis, severe sepsis and septic shock, respectively, and were statistically superior to those of control patients. Procalcitonin was gradually diminished over time with the resolution of the syndrome, while it was sustained in the same or more augmented levels upon worsening. Mean concentrations of procalcitonin on the 1st day for patients finally progressing to ARDS, to ARDS and acute renal failure, to ARDS, acute renal failure and DIC and to ARDS, acute renal failure, DIC and hepatic failure were 10.48, 8.08, 32.72 and 43.35 ng/ml, respectively. ROC curves of the sensitivity and specificity of procalcitonin for the evaluation of SIRS and sepsis were similar.Conclusions: The definite differential diagnosis between SIRS and sepsis may not rely on a single application of procalcitonin but on the complete clinical and laboratory evaluation of the patient with procalcitonin playing a considerable role. Procalcitonin is an early prognostic marker of the advent of MODS; therefore, daily determinations might help in the follow-up of the critically ill patient. [ABSTRACT FROM AUTHOR]

Objective. A prominent feature of sepsis is dysfunction of the microcirculation, with impaired perfusion and regional tissue oxygenation causing a deficit in oxygen extraction. If shunting of oxygen transport past closed hypoxic microcirculatory beds is responsible for this, vasodilator therapy, which raises the driving pressure of the microcirculation and thereby promotes flow, could recruit such shunted microcirculatory units and improve tissue oxygenation. Design. A literature search was conducted in Medline for evidence of this expected benefit of vasodilators in sepsis. Methods. Studies were searched using the keyword for vasodilating drugs in combination with "sepsis," "septic," "multiple organ failure," or "critically ill patients." The search included animal and clinical investigations but only where the effects of vasodilator therapy were demonstrated by regional measures of oxygen transport variables (e.g., oxygen extraction variables, regional ischemia, microcirculatory flow or tissue oxygenation measurements). The vasodilating drugs investigated included prostacyclin, pentoxifylline, N-acetyl-cysteine, and nitric oxide donors used in animal and human sepsis. Results. Prostacyclin and nitric oxide donors are the best studied vasodilating agents in experimental sepsis and have shown improved tissue perfusion and oxygen extraction. In several clinical studies prostacyclin has also been shown to have such beneficial effects. Recent studies using orthogonal polarization spectral imaging have shown microcirculatory recruitment by nitric oxide donors in hemodynamically resuscitated septic patients. Whether such therapeutic modalities aimed at recruitment of the microcirculation improve outcome, however, still has to be determined. [ABSTRACT FROM AUTHOR]