Evaluating tissue hypoxia and the response to fluid administration in septic shock patients: a metabolic cluster analysis.

BACKGROUND: The selection of adequate indicators of tissue hypoxia for guiding the resuscitation process of septic patients is a highly relevant issue. Current guidelines advocate for the use of lactate as sole metabolic marker, which may be markedly limited, and the integration of different variables seems more adequate. In this study, we explored the metabolic profile and its implications in the response to the administration of a fluid challenge in early septic shock patients. METHODS: Observational study including septic shock patients within 24 h of ICU admission, monitored with a cardiac output estimation system, with ongoing resuscitation. Hemodynamic and metabolic variables were measured before and after a fluid challenge (FC). A two-step cluster analysis was used to define the baseline metabolic profile, including lactate, central venous oxygen saturation (ScvO2), central venous-to-arterial carbon dioxide difference (PcvaCO2), and PcvaCO2 corrected by the difference in arterial-to-venous oxygen content (PcvaCO2/CavO2). RESULTS: Seventy-seven fluid challenges were analyzed. Cluster analysis revealed two distinct metabolic profiles at baseline. Cluster A exhibited lower ScvO2, higher PcvaCO2, and lower PcvaCO2/CavO2. Increases in cardiac output (CO) were associated with increases in VO2 exclusively in cluster A. Baseline isolated metabolic variables did not correlate with VO2 response, and changes in ScvO2 and PcvaCO2 were associated to VO2 increase only in cluster A. CONCLUSIONS: In a population of early septic shock patients, two distinct metabolic profiles were identified, suggesting tissue hypoxia or dysoxia. Integrating metabolic variables enhances the ability to detect those patients whose VO2 might increase as results of fluid administration.

Altered Microvascular Reactivity During a Skin Thermal Challenge Is Associated With Organ Dysfunction and Slow Recovery After Cardiac Surgery.

OBJECTIVES: To assess microvascular reactivity during a skin thermal challenge early post-cardiac surgery and its association with outcomes. DESIGN: Noninvasive physiological study. SETTING: Thirty-five-bed department of intensive care. PARTICIPANTS: Patients admitted to the intensive care unit post-cardiac surgery. INTERVENTIONS: Thermal challenge. MEASUREMENTS AND MAIN RESULTS: A total of 46 patients were included; 14 needed vasoactive or ventilatory support for at least 48 hours (slow recovery), and 32 had a more rapid recovery. Skin blood flow (SBF) was measured on the anterior proximal forearm using skin laser Doppler. A thermal challenge was performed by abruptly increasing local skin temperature from 37°C to 43°C while monitoring SBF. The ratio between SBFs at 43°C and 37°C was calculated to measure microvascular reactivity. SBF at 37°C was not significantly different in patients with a slow recovery and those with a rapid recovery, but SBF after 9 minutes at 43°C was lower (48.5 [17.3-69.0] v 85.1 [45.2-125.7], p < 0.01), resulting in a lower SBF ratio (2.8 [1.5-4.7] v 4.8 [3.7-7.8], p < 0.01). Patients with lower SBF ratios were more likely to have dysfunction of at least one organ (assessed using the sequential organ dysfunction score) 48 hours post-cardiac surgery than those with higher ratios: 88% versus 40% versus 27% (p < 0.01), respectively, for the lowest, middle, and highest tertiles of SBF ratio. In multivariable analysis, a lower SBF ratio was an independent risk factor for slow recovery. CONCLUSIONS: Early alterations in microvascular reactivity, evaluated by a skin thermal challenge, are correlated with organ dysfunction. These observations may help in the development of new, simple, noninvasive monitoring systems in postoperative patients.

The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (pCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study.

How to cite this article: Sundarsingh V, Kumar M, Rodrigues PR. The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (pCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study. Indian J Crit Care Med 2024;28(7):709.

The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study.

Introduction: The usual methods of perfusion assessment in patients with shock, such as capillary refill time, skin mottling, and serial serum lactate measurements have many limitations. Veno-arterial difference in the partial pressure of carbon dioxide (PCO2 gap) is advocated being more reliable. We evaluated serial change in PCO2 gap during resuscitation in circulatory shock and its effect on ICU outcomes. Materials and methods: This prospective observational study included 110 adults with circulatory shock. Patients were resuscitated as per current standards of care. We recorded invasive arterial pressure, urine output, cardiac index (CI), PCO2 gap at ICU admission at 6, 12, and 24 hours, and various patient outcomes. Results: Significant decrease in PCO2 gap was observed at 6 h and was accompanied by improvement in serum lactate, mean arterial pressure, CI and urine output in (n = 61). We compared these patients with those in whom this decrease did not occur (n = 49). Mortality and ICU LOS was significantly lower in patients with low PCO2 gap, while more patients with high PCO2 gap required RRT. Conclusion: We found that a persistently high PCO2 gap at 6 and 12 h following resuscitation in patients with shock of various etiologies, was associated with increased mortality, need for RRT and increased ICU LOS. High PCO2 gap had a moderate discriminative ability to predict mortality. How to cite this article: Zirpe KG, Tiwari AM, Kulkarni AP, Vaidya HS, Gurav SK, Deshmukh AM, et al. The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study. Indian J Crit Care Med 2024;28(4):349-354.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

INTRODUCTION: Microcirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. METHODS: Adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. RESULTS: Of 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). CONCLUSIONS: Poor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Obstructive Shock, from Diagnosis to Treatment.

Shock is a life threatening pathological condition characterized by inadequate tissue oxygen supply. Four different subgroups of shock have been proposed according to the mechanism causing the shock. Of these, obstructive shock is characterized by reduction in cardiac output due to noncardiac diseases. The most recognized causes include pulmonary embolism, tension pneumothorax, pericardial tamponade and aortic dissection. Since obstructive shock typically cannot be stabilized unless cause for shock is resolved, diagnosis of the underlying disease is eminent. In this review, we therefore focus on diagnosis of obstructive shock and suggest a structured approach in three steps including clinical examination, ultrasound examination using the rapid ultrasound in shock (RUSH) protocol and radiological imaging if needed.

Early versus delayed enteral nutrition in mechanically ventilated patients with circulatory shock: a nested cohort analysis of an international multicenter, pragmatic clinical trial.

INTRODUCTION: Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. METHODS: We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating < 48 h from ICU admission and DEN > 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site. RESULTS: We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18-93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups. CONCLUSION: In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.

A new physiologic-based integrated algorithm in the management of neonatal hemodynamic instability.

Physiologic-based management of hemodynamic instability is proven to guide the logical selection of cardiovascular support and shorten the time to clinical recovery compared to an empiric approach that ignores the heterogeneity of the hemodynamic instability related mechanisms. In this report, we classified neonatal hemodynamic instability, circulatory shock, and degree of compensation into five physiologic categories, based on different phenotypes of blood pressure (BP), other clinical parameters, echocardiography markers, and oxygen indices. This approach is focused on hemodynamic instability in infants with normal cardiac anatomy.Conclusion: The management of hemodynamic instability is challenging due to the complexity of the pathophysiology; integrating different monitoring techniques is essential to understand the underlying pathophysiologic mechanisms and formulate a physiologic-based medical recommendation and approach. What is Known: • Physiologic-based assessment of hemodynamics leads to targeted and pathophysiologic-based medical recommendations. What is New: • Hemodynamic instability in neonates can be categorized according to the underlying mechanism into five main categories, based on blood pressure phenotypes, systemic vascular resistance, and myocardial performance. • The new classification helps with the targeted management and logical selection of cardiovascular support.

Biochemical markers for clinical monitoring of tissue perfusion.

The assessment and monitoring of the tissue perfusion is extremely important in critical conditions involving circulatory shock. There is a wide range of established methods for the assessment of cardiac output as a surrogate of oxygen delivery to the peripheral tissues. However, the evaluation of whether particular oxygen delivery is sufficient to ensure cellular metabolic demands is more challenging. In recent years, specific biochemical parameters have been described to indicate the status between tissue oxygen demands and supply. In this review, the authors summarize the application of some of these biochemical markers, including mixed venous oxygen saturation (SvO2), lactate, central venous-arterial carbon dioxide difference (PCO2 gap), and PCO2 gap/central arterial-to-venous oxygen difference (Ca-vO2) for hemodynamic assessment of tissue perfusion. The thorough monitoring of the adequacy of tissue perfusion and oxygen supply in critical conditions is essential for the selection of the most appropriate therapeutic strategy and it is associated with improved clinical outcomes.

Near-Infrared Spectroscopy in Adult Circulatory Shock: A Systematic Review.

BACKGROUND: Circulatory shock affects every third patient in intensive care units and is associated with high mortality. Near-infrared spectroscopy (NIRS) could serve as a means for monitoring tissue perfusion in circulatory shock. PURPOSE: To assess the evidence of NIRS monitoring in circulatory shock, we conducted a systematic review of the literature. METHODS: The study protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO). We searched PubMed, Ovid MEDLINE, Scopus, and EBM Reviews databases. The reference lists of included articles, last volumes of key journals, and NIRS monitor manufacturers' webpages were searched manually. Two reviewers independently selected included studies. The quality of studies was assessed. The qualitative synthesis was guided by 3 questions: First, does NIRS monitoring improve patient-centered outcomes in adult circulatory shock patient? Second, do NIRS-derived parameters predict patient-centered outcomes, such as mortality and organ dysfunction, and third, does NIRS monitoring give additional information to guide treatment decisions? MAIN RESULTS: Eighteen observational studies with 927 patients were included. Because of considerable clinical heterogeneity of the data, we were not able to perform a meta-analysis. Also, due to lack of randomized controlled trials, the first review question could not be answered. Based on the current review, baseline tissue oxygen saturation (StO2) however seems to predict mortality and identify patients with most severe forms of circulatory shock. CONCLUSIONS: Near-infrared spectroscopy-derived StO2 can predict mortality in circulatory shock, but high-quality data on the impact of NIRS monitoring are lacking. Furthermore, the marked heterogeneity of the studies makes combining the results of individual studies difficult. Standardization of methodology and clinical randomized trials are needed before wider clinical use.

A longitudinal study highlights shared aspects of the transcriptomic response to cardiogenic and septic shock.

BACKGROUND: Septic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock. METHODS: We performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value < 0.01 (Benjamini-Hochberg multiple test correction) were defined differentially expressed (DEGs). We used gene set enrichment analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock. RESULTS: In both CS and SS patients, GO terms of inflammatory response and pattern recognition receptors (PRRs) were downregulated following ICU admission, whereas gene sets of DNA replication were upregulated. At the gene level, we observed that alarmins, interleukin receptors, PRRs, inflammasome, and DNA replication genes significantly changed their expression in CS and SS, but not in SC. Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend. CONCLUSIONS: This pilot study supports, within the limits of a small sample size, the role of alarmins, PRRs, DNA replication, and immunoglobulins in the pathophysiology of circulatory shock, either in the presence of infection or not. We hypothesize that these genes could be potential targets of therapeutic interventions in CS and SS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02141607. Registered 19 May 2014.

Capillary refill time variation induced by passive leg raising predicts capillary refill time response to volume expansion.

BACKGROUND: A peripheral perfusion-targeted resuscitation during early septic shock has shown encouraging results. Capillary refill time, which has a prognostic value, was used. Adding accuracy and predictability on capillary refill time (CRT) measurement, if feasible, would benefit to peripheral perfusion-targeted resuscitation. We assessed whether a reduction of capillary refill time during passive leg raising (ΔCRT-PLR) predicted volume-induced peripheral perfusion improvement defined as a significant decrease of capillary refill time following volume expansion. METHODS: Thirty-four patients with acute circulatory failure were selected. Haemodynamic variables, metabolic variables (PCO2gap), and four capillary refill time measurements were recorded before and during a passive leg raising test and after a 500-mL volume expansion over 20 min. Receiver operating characteristic curves were built, and areas under the curves were calculated (ROCAUC). Confidence intervals (CI) were performed using a bootstrap analysis. We recorded mortality at day 90. RESULTS: The least significant change in the capillary refill time was 25% [95% CI, 18-30]. We defined CRT responders as patients showing a reduction of at least 25% of capillary refill time after volume expansion. A decrease of 27% in ΔCRT-PLR predicted peripheral perfusion improvement with a sensitivity of 87% [95% CI, 73-100] and a specificity of 100% [95% CI, 74-100]. The ROCAUC of ΔCRT-PLR was 0.94 [95% CI, 0.87-1.0]. The ROCAUC of baseline capillary refill time was 0.73 [95% CI, 0.54-0.90] and of baseline PCO2gap was 0.79 [0.61-0.93]. Capillary refill time was significantly longer in non-survivors than in survivors at day 90. CONCLUSION: ΔCRT-PLR predicted peripheral perfusion response following volume expansion. This simple low-cost and non-invasive diagnostic method could be used in peripheral perfusion-targeted resuscitation protocols. TRIAL REGISTRATION: CPP Lyon Sud-Est II ANSM: 2014-A01034-43 Clinicaltrial.gov, NCT02248025 , registered 13th of September 2014.

Respiratory quotient estimations as additional prognostic tools in early septic shock.

Central venous-to-arterial carbon dioxide difference (PcvaCO2), and its correction by the arterial-to-venous oxygen content difference (PcvaCO2/CavO2) have been proposed as additional tools to evaluate tissue hypoxia. Since the relationship between pressure and content of CO2 (CCO2) might be affected by several factors, some authors advocate for the use of CcvaCO2/CavO2. The aim of the present study was to explore the factors that might intervene in the difference between PcvaCO2/CavO2 and CcvaCO2/CavO2, and to analyze their association with mortality. Observational study in a 30-bed mixed ICU. Fifty-two septic shock patients within the first 24 h of ICU admission were studied. After restoration of mean arterial pressure, hemodynamic and metabolic parameters were evaluated. A total of 110 sets of measurements were performed. Simultaneous PcvaCO2/CavO2 and CcvaCO2/CavO2 values were correlated, but agreement analysis showed a significant proportional bias. The difference between PcvaCO2/CavO2 and CcvaCO2/CavO2 was independently associated with pH, ScvO2, baseline CcvaCO2/CavO2 and hemoglobin. A stepwise regression analysis showed that pH was the single best predictor for the magnitude of such difference, with very limited effect of other variables. At inclusion, variables associated with ICU-mortality were lactate, pH, PcvaCO2/CavO2, and the difference between PcvaCO2/CavO2 and CcvaCO2/CavO2. Initial ScvO2, PcvaCO2, CcvaCO2/CavO2, and cardiac index were not different in survivors and non-survivors. In a population of early septic shock patients, simultaneous values of PcvaCO2/CavO2 and CcvaCO2/CavO2 were not equivalent, and the main determinant of the magnitude of the difference between these two parameters was pH. The PcvaCO2/CavO2 ratio was associated with ICU mortality, whereas CcvaCO2/CavO2 was not.

Central venous-to-arterial carbon dioxide difference and the effect of venous hyperoxia: A limiting factor, or an additional marker of severity in shock?

Central venous-to-arterial carbon dioxide difference (PcvaCO2) has demonstrated its prognostic value in critically ill patients suffering from shock, and current expert recommendations advocate for further resuscitation interventions when PcvaCO2 is elevated. PcvaCO2 combination with arterial-venous oxygen content difference (PcvaCO2/CavO2) seems to enhance its performance when assessing anaerobic metabolism. However, the fact that PCO2 values might be altered by changes in blood O2 content (the Haldane effect), has been presented as a limitation of PCO2-derived variables. The present study aimed at exploring the impact of hyperoxia on PcvaCO2 and PcvaCO2/CavO2 during the early phase of shock. Prospective interventional study. Ventilated patients suffering from shock within the first 24 h of ICU admission. Patients requiring FiO2 ≥ 0.5 were excluded. At inclusion, simultaneous arterial and central venous blood samples were collected. Patients underwent a hyperoxygenation test (5 min of FiO2 100%), and arterial and central venous blood samples were repeated. Oxygenation and CO2 variables were calculated at both time points. Twenty patients were studied. The main cause of shock was septic shock (70%). The hyperoxygenation trial increased oxygenation parameters in arterial and venous blood, whereas PCO2 only changed at the venous site. Resulting PcvaCO2 and PcvaCO2/CavO2 significantly increased [6.8 (4.9, 8.1) vs. 7.6 (6.7, 8.5) mmHg, p 0.001; and 1.9 (1.4, 2.2) vs. 2.3 (1.8, 3), p < 0.001, respectively]. Baseline PcvaCO2, PcvaCO2/CavO2 and ScvO2 correlated with the magnitude of PO2 augmentation at the venous site within the trial (ρ -0.46, p 0.04; ρ 0.6, p < 0.01; and ρ 0.7, p < 0.001, respectively). Increased PcvaCO2/CavO2 values were associated with higher mortality in our sample [1.46 (1.21, 1.89) survivors vs. 2.23 (1.86, 2.8) non-survivors, p < 0.01]. PcvaCO2 and PcvaCO2/CavO2 are influenced by oxygenation changes not related to flow. Elevated PcvaCO2 and PcvaCO2/CavO2 values might not only derive from cardiac output inadequacy, but also from venous hyperoxia. Elevated PcvaCO2/CavO2 values were associated with higher PO2 transmission to the venous compartment, suggesting higher shunting phenomena.

Role of Urinary Neutrophil Gelatinase-associated Lipocalin as a Biomarker of Acute Kidney Injury in Patients with Circulatory Shock.

BACKGROUND: The early prediction of acute kidney injury (AKI) by the current clinical and laboratory methods remains inadequate. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a promising noninvasive biomarker of kidney injury in shock. The aim of this study was to assess the ability of urinary NGAL (uNGAL) to predict AKI in adult Intensive Care Unit (ICU) patients. MATERIALS AND METHODS: We prospectively studied 70 patients with circulatory shock admitted to the ICU over a period of 1 year. uNGAL was analyzed at ICU admission and after 24 h. Risk, injury, failure, loss, and end-stage kidney criteria were calculated at admission and for consecutive 4 days. The primary outcome was AKI defined as an increase in creatinine of at least 50% from baseline or a reduction in urine output to <0.5 ml/kg/h for 6 h. RESULTS: uNGAL was a good diagnostic marker for AKI development; at day 1, the cutoff value 48.54 ng/mL had a sensitivity and specificity of 79.49 and 73.14, respectively, and the area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.75-0.87) for predicting AKI. At day 2, the cutoff value 190.92 ng/mL had a sensitivity and specificity of 90.0 and 64.66, respectively, and the AUC of 0.76 (95% CI, 0.70-0.88) for predicting AKI. CONCLUSION: uNGAL could be a good early predictor biomarker of AKI following circulatory shock.

Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure.

AIM: More than 7000 male circumcisions are performed in Scandinavia every year. Circumcision is regulated in different ways in Sweden and Denmark and Norway. This study reviewed and described factors associated with complications of circumcision in infant boys in Scandinavia over the last two decades and discussed how these complications could be avoided. METHODS: Data on significant complications following circumcision on boys under the age of one in Scandinavia over the last 20 years were collected. Information was retrieved from testimonies of circumcisers, witnesses, medical records and verdicts. A systematic review was performed of fatal cases in the literature. RESULTS: We found that 32 cases had been reported to the health authorities in the three countries, and we identified a total of 74 complications in these cases. These included four boys with severe bleeding and circulatory shock, which ended in the death of one boy. Other less serious complications may have occurred in other boys, but not been reported. CONCLUSION: Complications following male circumcision in Scandinavia were relatively rare, but serious complications did occur. Based on the analyses of the severe cases, we argue that circumcision should only be performed at hospitals with 24-hour emergency departments.

Near infrared spectroscopy (NIRS) to assess the effects of local ischemic preconditioning in the muscle of healthy volunteers and critically ill patients.

Near-infrared spectroscopy (NIRS) permits non-invasive evaluation of tissue oxygen saturation (StO2). A vascular occlusion test (VOT) produces transient controlled ischemia similar to that used in ischemic preconditioning. We hypothesized that we could evaluate local responses to ischemic preconditioning by performing repeated VOTs and observing the changes in different NIRS VOT-derived variables. In healthy volunteers (n=20), four VOTs were performed at 30-min intervals on one day and, in a second group (n=21), two VOTs with time intervals of 5, 15 or 30min were performed on 3 separate days. Two cohorts of patients, one with circulatory shock (n=23) and a hemodynamically stable group (n=20), were also studied, repeating the VOT twice with a 5-min interval. In the 1-day volunteers, there was a median decrease of 15 (6-21)% in the Desc slope (StO2 decrease during VOT) after the second VOT, but no significant change in the Asc slope (StO2 increase after VOT). In the 3-day volunteers, the Desc slope also decreased, regardless of the time interval between VOTs. There was no overall decrease in the Desc slope in either patient cohort with repeated VOTs but there was marked individual patient variability. Patients in whom the Desc slope decreased had less organ dysfunction at admission, required less norepinephrine (0.00 vs 0.08mcg/kg/min, p=0.02), less frequently had sepsis (12 vs 50%, p=0.02) and had a lower mortality (6 vs 39%, p=0.03) compared to those in whom it did not decrease. Repeated NIRS VOT can non-invasively assess the local effects of ischemic preconditioning in the muscle.

High and intermediate risk pulmonary embolism in the ICU.

Pulmonary embolism (PE) is a common and important medical emergency, encountered by clinicians across all acute care specialties. PE is a relatively uncommon cause of direct admission to the intensive care unit (ICU), but these patients are at high risk of death. More commonly, patients admitted to ICU develop PE as a complication of an unrelated acute illness. This paper reviews the epidemiology, diagnosis, risk stratification, and particularly the management of PE from a critical care perspective. Issues around prevention, anticoagulation, fibrinolysis, catheter-based techniques, surgical embolectomy, and extracorporeal support are discussed.

The physiological basis for individualized oxygenation targets in critically ill patients with circulatory shock.

BACKGROUND: Circulatory shock, defined as decreased tissue perfusion, leading to inadequate oxygen delivery to meet cellular metabolic demands, remains a common condition with high morbidity and mortality. Rapid restitution and restoration of adequate tissue perfusion are the main treatment goals. To achieve this, current hemodynamic strategies focus on adjusting global physiological variables such as cardiac output (CO), hemoglobin (Hb) concentration, and arterial hemoglobin oxygen saturation (SaO2). However, it remains a challenge to identify optimal targets for these global variables that best support microcirculatory function. Weighting up the risks and benefits is especially difficult for choosing the amount of oxygen supplementation in critically ill patients. This review assesses the physiological basis for oxygen delivery to the tissue and provides an overview of the relevant literature to emphasize the importance of considering risks and benefits and support decision making at the bedside. PHYSIOLOGICAL PREMISES: Oxygen must reach the tissue to enable oxidative phosphorylation. The human body timely detects hypoxia via different mechanisms aiming to maintain adequate tissue oxygenation. In contrast to the pulmonary circulation, where the main response to hypoxia is arteriolar vasoconstriction, the regulatory mechanisms of the systemic circulation aim to optimize oxygen availability in the tissues. This is achieved by increasing the capillary density in the microcirculation and the capillary hematocrit thereby increasing the capacity of oxygen diffusion from the red blood cells to the tissue. Hyperoxia, on the other hand, is associated with oxygen radical production, promoting cell death. CURRENT STATE OF RESEARCH: Clinical trials in critically ill patients have primarily focused on comparing macrocirculatory endpoints and outcomes based on stroke volume and oxygenation targets. Some earlier studies have indicated potential benefits of conservative oxygenation. Recent trials show contradictory results regarding mortality, organ dysfunction, and ventilatory-free days. Empirical studies comparing various targets for SaO2, or partial pressure of oxygen indicate a U-shaped curve balancing positive and negative effects of oxygen supplementation. CONCLUSION AND FUTURE DIRECTIONS: To optimize risk-benefit ratio of resuscitation measures in critically ill patients with circulatory shock in addition to individual targets for CO and Hb concentration, a primary aim should be to restore tissue perfusion and avoid hyperoxia. In the future, an individualized approach with microcirculatory targets will become increasingly relevant. Further studies are needed to define optimal targets.

Episodic idiopathic systemic capillary leak syndrome in a girl.

Episodic idiopathic systemic capillary leak syndrome is a rare disorder that presents with attacks of circulatory shock due to plasma leakage into the extravascular space. Reported here is the case of a girl who had recurrent circulatory shock. The diagnosis of episodic idiopathic systemic capillary leak syndrome was made following the fourth episode. The course was favorable following acute i.v. cristalloids and methylprednisolone.