Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

Introduction

Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (P_btO₂) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH).

Methods

We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and P_btO₂ were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs).

Results

One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. P_btO₂ decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (P_btO₂ <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. P_btO₂ <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion.

Conclusions

Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH.     

Elevated plasma thrombomodulin and angiopoietin-2 predict the development of acute kidney injury in patients with acute myocardial infarction

Introduction

Acute kidney injury (AKI) following acute myocardial infarction (AMI) is associated with unfavorable prognosis. Endothelial activation and injury were found to play a critical role in the development of both AKI and AMI. This pilot study aimed to determine whether the plasma markers of endothelial injury and activation could serve as independent predictors for AKI in patients with AMI.

Methods

This prospective study was conducted from March 2010 to July 2012 and enrolled consecutive 132 patients with AMI receiving percutaneous coronary intervention (PCI). Plasma levels of thrombomodulin (TM), von Willebrand factor (vWF), angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) were measured on day 1 of AMI. AKI was defined as elevation of serum creatinine of more than 0.3 mg/dL within 48 hours.

Results

In total, 13 out of 132 (9.8%) patients with AMI developed AKI within 48 hours. Compared with patients without AKI, patients with AKI had increased plasma levels of Ang-2 (6338.28 ± 5862.77 versus 2412.03 ± 1256.58 pg/mL, P = 0.033) and sTM (7.6 ± 2.26 versus 5.34 ± 2.0 ng/mL, P < 0.001), and lower estimated glomerular filtration rate (eGFR) (46.5 ± 20.2 versus 92.5 ± 25.5 mL/min/1.73 m², P < 0.001). Furthermore, the areas under the receiver operating curves demonstrated that plasma thrombomodulin (TM) and Ang-2 levels on day 1 of AMI had modest discriminative powers for predicting AKI development following AMI (0.796, P <0.001; 0.833, P <0.001; respectively).

Conclusions

Endothelial activation, quantified by plasma levels of TM and Ang-2 may play an important role in development of AKI in patients with AMI.     

Racemic ketamine in adult head injury patients: use in endotracheal suctioning

Introduction

Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless, its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation (SjO₂) and cerebral blood flow velocity (mVMCA) before and after the administration of ketamine.

Methods

In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS.

Results

In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P <0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P <0.001), SjO₂ (from 82.3 ± 7.5 to 89.1 ± 5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO₂ were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs. 11.0 ± 6.4 mmHg; P <0.05). Cough score was significantly reduced in comparison with controls (P <0.0001).

Conclusions

Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO₂, and prevented cough reflex. Nevertheless, ketamine was not completely effective when used to control ICP increase after administration of 100 γ/kg/min for 10 minutes.     

An Internet-Based Diabetes Management Platform Improves Team Care and Outcomes in an Urban Latino Population

OBJECTIVE

To compare usual diabetes care (UDC) to a comprehensive diabetes care intervention condition (IC) involving an Internet-based “diabetes dashboard” management tool used by clinicians.

RESEARCH DESIGN AND METHODS

We used a parallel-group randomized design. Diabetes nurses, diabetes dietitians, and providers used the diabetes dashboard as a clinical decision support system to deliver a five-visit, 6-month intervention to 199 poorly controlled (HbA_1c >7.5% [58 mmol/mol]) Latino type 2 diabetic (T2D) patients (mean age 55 years, 60% female) at urban community health centers. We compared this intervention to an established, in-house UDC program (n = 200) for its impact on blood glucose control and psychosocial outcomes.

RESULTS

Recruitment and retention rates were 79.0 and 88.5%, respectively. Compared with UDC, more IC patients reached HbA_1c targets of <7% (53 mmol/mol; 15.8 vs. 7.0%, respectively, P < 0.01) and <8% (64 mmol/mol; 45.2 vs. 25.3%, respectively, P < 0.001). In multiple linear regression adjusting for baseline HbA_1c, adjusted mean ± SE HbA_1c at follow-up was significantly lower in the IC compared with the UDC group (P < 0.001; IC 8.4 ± 0.10%; UDC 9.2 ± 0.10%). The results showed lower diabetes distress at follow-up for IC patients (40.4 ± 2.1) as compared with UDC patients (48.3 ± 2.0) (P < 0.01), and also lower social distress (32.2 ± 1.3 vs. 27.2 ± 1.4, P < 0.01). There was a similar, statistically significant (P < 0.01) improvement for both groups in the proportion of patients moving from depressed status at baseline to nondepressed at follow-up (41.8 vs. 40%; no significance between groups).

CONCLUSIONS

The diabetes dashboard intervention significantly improved diabetes-related outcomes among Latinos with poorly controlled T2D compared with a similar diabetes team condition without access to the diabetes dashboard.     

Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis

OBJECTIVE

Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor–based overnight predictive low-glucose suspend (PLGS) system.

RESEARCH DESIGN AND METHODS

In two age-groups of children with type 1 diabetes (11–14 and 4–10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight.

RESULTS

Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11–14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4–10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11–14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4–10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis.

CONCLUSIONS

In 4–14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher.     

The consequences of sudden fluid shifts on body composition in critically ill patients

Introduction

Estimation of body composition as fat-free mass (FFM) is subjected to many variations caused by injury and stress conditions in the intensive care unit (ICU). Body cell mass (BCM), the metabolically active part of FFM, is reported to be more specifically correlated to changes in nutritional status. Bedside estimation of BCM could help to provide more valuable markers of nutritional status and may promote understanding of metabolic consequences of energy deficit in the ICU patients. We aimed to quantify BCM, water compartments and FFM by methods usable at the bedside for evaluating the impact of sudden and massive fluid shifts on body composition in ICU patients.

Methods

We conducted a prospective experimental study over an 6 month-period in a 18-bed ICU. Body composition of 31 consecutive hemodynamically stable patients requiring acute renal replacement therapy for fluid overload (ultrafiltration ≥5% body weight) was investigated before and after the hemodialysis session. Intra-(ICW) and extracellular (ECW) water volumes were calculated from the raw values of the low- and high-frequency resistances measured by multi-frequency bioelectrical impedance. BCM was assessed by a calculated method recently developed for ICU patients. FFM was derived from BCM and ECW.

Results

Intradialytic weight loss was 3.8 ± 0.8 kg. Percentage changes of ECW (-7.99 ± 4.60%) and of ICW (-7.63 ± 5.11%) were similar, resulting ECW/ICW ratio constant (1.26 ± 0.20). The fall of FFM (-2.24 ± 1.56 kg, -4.43 ± 2.65%) was less pronounced than the decrease of ECW (P < 0.001) or ICW (P < 0.001). Intradialytic variation of BCM was clinically negligible (-0.38 ± 0.93 kg, -1.56 ± 3.94%) and was significantly less than FFM (P < 0.001).

Conclusions

BCM estimation is less driven by sudden massive fluid shifts than FMM. Assessment of BCM should be preferred to FFM when severe hydration disturbances are present in ICU patients.     

Evaluation of 3D blood flow patterns and wall shear stress in the normal and dilated thoracic aorta using flow-sensitive 4D CMR

Background

The purpose of this study was to investigate 3D flow patterns and vessel wall parameters in patients with dilated ascending aorta, age-matched subjects, and healthy volunteers.

Methods

Thoracic time-resolved 3D phase contrast CMR with 3-directional velocity encoding was applied to 33 patients with dilated ascending aorta (diameter ≥40 mm, age=60±16 years), 15 age-matched normal controls (diameter ≤37 mm, age=68±7.5 years) and 15 young healthy volunteers (diameter ≤30 mm, age=23±2 years). 3D blood flow was visualized and flow patterns were graded regarding presence of supra-physiologic-helix and vortex flow using a semi-quantitative 3-point grading scale. Blood flow velocities, regional wall shear stress (WSS), and oscillatory shear index (OSI) were quantified.

Results

Incidence and strength of supra-physiologic-helix and vortex flow in the ascending aorta (AAo) was significantly higher in patients with dilated AAo (16/33 and 31/33, grade 0.9±1.0 and 1.5±0.6) than in controls (2/15 and 7/15, grade 0.2 ± 0.6 and 0.6 ± 0.7, P<.05) or healthy volunteers (1/15 and 0/15, grade 0.1 ± 0.3 P<.05). Greater strength of the ascending aortic helix and vortex flow were associated with significant differences in AAo diameters (P<.05). Peak systolic WSS in the ascending aorta and aortic arch was significantly lower in patients with dilated AAo (P<.0157-.0488). AAo diameter positively correlated to time to peak systolic velocities (r=0.30-0.53, P<.04), OSI (r=0.33-0.49, P<0.02) and inversely correlated to peak systolic WSS (r=0.32-0.40, P<.03). Peak systolic WSS was significantly lower in AAo aneurysms at the right and outer curvature within the AAo and proximal arch (P<.01-.05).

Conclusions

Increase in AAo diameter is significantly correlated with the presence and strength of supra-physiologic-helix and vortex formation in the AAo, as well with decrease in systolic WSS and increase in OSI.     

Early changes of plasma angiopoietin-2 in patients with multiple trauma

BACKGROUND:

This study was undertaken to investigate the early changes of plasma levels of angiopoietin-2 (Ang-2) in patients with multiple trauma and the relations of plasma Ang-2, endothelial injury, and prognosis.

METHODS:

This study comprised 59 patients with multiple trauma who had been treated at the emergency department of Liao Cheng People’s Hospital from January 2008 to January 2010. Among them, 36 were male and 23 female. Their average age was 32.3±11.5 years. The 59 patients were divided into a severe trauma group (ISS≥16 points, 29 patients) and a slight trauma group (ISS<16 points, 30 patients) by injury severity score (ISS). Thirty healthy people aged more than 18 years with an average of 33.5±10.6 years served as controls (19 male and 11 female). Peripheral blood (10 mL) was collected within 10 minutes after the patients arrived at the emergency department, and plasma was separated from the blood. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of angiopoietin 2, thrombomodulin (TM), and Von willebrand factor (vWF).

RESULTS:

The level of Ang-2 in the severe trauma group (ISS score≥16 points) was significantly higher than that in the slight trauma group (ISS score<16 points) (P<0.05). The levels in the two groups were significantly higher than those in the control group (P<0.05). The levels of angiopoietin-2 in deaths were significantly higher than those in survivors (P<0.05). The levels of angiopoietin-2 were significantly correlated with the levels of vWF and TM (P<0.05).

CONCLUSIONS:

The plasma levels of Ang-2 are significantly higher after multiple trauma, and correlated with the degree of trauma severity. The levels of angiopoietin-2 are correlated with endothelial injury after multiple trauma, and are important values for the prognosis of patients with multiple trauma.KEY WORDS: Multiple trauma, Angiopoietin-2, Endothelial injury, Prognosis     

Effects of Fixed and Removable Space Maintainers on Plaque Accumulation,Periodontal Health,Candidal and Enterococcus Faecalis Carriage

Objective

To evaluate the effects of space maintainers on plaque accumulation, periodontal health and oral microflora.

Subjects and Methods

The study participants comprised 38 patients aged 4-10 years requiring either fixed or removable space maintainers. Plaque index, gingival index, bleeding on probing index, candidal colonization and Enterococcus faecalis were recorded just before the application of space maintainers (T0) and during treatment at the 1st (T1), 3rd (T2) and 6th (T3) month.

Results

The gingival and bleeding on probing index scores increased significantly (gingival index from 0.20 ± 0254 to 0.54 ± 0417 and bleeding on probing index from 7.18 ± 9.946 to 18.07 ± 14.074) in the regions with fixed space maintainers at T3 (p < 0.01). The mean Candida counts also increased (for removable appliances from 1.90 ± 3.638 to 1.98 ± 3.318, p < 0.05, and for fixed appliances from 4.25 ± 4.587 to 4.52 ± 4.431, p < 0.001). The salivary E. faecalis counts at T3 also increased significantly with the use of fixed and removable appliances (for removable appliances from 5.93 ± 2.65 to 85.53 ± 34.1 and for fixed appliances from 4.95 ± 2.94 to 123.59 ± 29.51, p < 0.001). A positive correlation was found between the plaque (r = 0.67), gingival (r = 0.76) and bleeding on probing index scores (r = 0.76) and the candidal colonization for the fixed space maintainers (p < 0.01, p < 0.001).

Conclusions

In this study, both fixed and removable space maintainers led to an increase in the number of microorganisms in the oral cavity as well as to increases in the periodontal index scores. Patients should be informed that space maintainers may serve as a source of infection and that special attention must be given to their oral hygiene.Key Words: Space maintainers, Periodontal health, <italic>Candida</italic>, <italic>Enterococcus faecalis</italic>     

Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients

Introduction

Higher body mass index (BMI) is associated with lower mortality in mechanically ventilated critically ill patients. However, it is yet unclear which body component is responsible for this relationship.

Methods

This retrospective analysis in 240 mechanically ventilated critically ill patients included adult patients in whom a computed tomography (CT) scan of the abdomen was made on clinical indication between 1 day before and 4 days after admission to the intensive care unit. CT scans were analyzed at the L3 level for skeletal muscle area, expressed as square centimeters. Cutoff values were defined by receiver operating characteristic (ROC) curve analysis: 110 cm² for females and 170 cm² for males. Backward stepwise regression analysis was used to evaluate low-muscle area in relation to hospital mortality, with low-muscle area, sex, BMI, Acute Physiologic and Chronic Health Evaluation (APACHE) II score, and diagnosis category as independent variables.

Results

This study included 240 patients, 94 female and 146 male patients. Mean age was 57 years; mean BMI, 25.6 kg/m². Muscle area for females was significantly lower than that for males (102 ± 23 cm² versus 158 ± 33 cm²; P < 0.001). Low-muscle area was observed in 63% of patients for both females and males. Mortality was 29%, significantly higher in females than in males (37% versus 23%; P = 0.028). Low-muscle area was associated with higher mortality compared with normal-muscle area in females (47.5% versus 20%; P = 0.008) and in males (32.3% versus 7.5%; P < 0.001). Independent predictive factors for mortality were low-muscle area, sex, and APACHE II score, whereas BMI and admission diagnosis were not. Odds ratio for low-muscle area was 4.3 (95% confidence interval, 2.0 to 9.0, P < 0.001). When applying sex-specific cutoffs to all patients, muscle mass appeared as primary predictor, not sex.

Conclusions

Low skeletal muscle area, as assessed by CT scan during the early stage of critical illness, is a risk factor for mortality in mechanically ventilated critically ill patients, independent of sex and APACHE II score. Further analysis suggests muscle mass as primary predictor, not sex. BMI is not an independent predictor of mortality when muscle area is accounted for.     

Better lactate clearance associated with good neurologic outcome in survivors who treated with therapeutic hypothermia after out-of-hospital cardiac arrest

Introduction

Several methods have been proposed to evaluate neurological outcome in out-of-hospital cardiac arrest (OHCA) patients. Blood lactate has been recognized as a reliable prognostic marker for trauma, sepsis, or cardiac arrest. The objective of this study was to examine the association between initial lactate level or lactate clearance and neurologic outcome in OHCA survivors who were treated with therapeutic hypothermia.

Methods

This retrospective cohort study included patients who underwent protocol-based 24-hour therapeutic hypothermia after OHCA between January 2010 and March 2012. Serum lactate levels were measured at the start of therapy (0 hours), and after 6 hours, 12 hours, 24 hours, 48 hours and 72 hours. The 6 hour and 12 hour lactate clearance were calculated afterwards. Patients’ neurologic outcome was assessed at one month after cardiac arrest; good neurological outcome was defined as Cerebral Performance Category one or two. The primary outcome was an association between initial lactate level and good neurologic outcome. The secondary outcome was an association between lactate clearance and good neurologic outcome in patients with initial lactate level >2.5 mmol/l.

Results

Out of the 76 patients enrolled, 34 (44.7%) had a good neurologic outcome. The initial lactate level showed no significant difference between good and poor neurologic outcome groups (6.07 ±4 .09 mmol/L vs 7.13 ± 3.99 mmol/L, P = 0.42), However, lactate levels at 6 hours, 12 hours, 24 hours, and 48 hours in the good neurologic outcome group were lower than in the poor neurologic outcome group (3.81 ± 2.81 vs 6.00 ± 3.22 P <0.01, 2.95 ± 2.07 vs 5.00 ± 3.49 P <0.01, 2.17 ± 1.24 vs 3.86 ± 3.92 P <0.01, 1.57 ± 1.02 vs 2.21 ± 1.35 P = 0.03, respectively). The secondary analysis showed that the 6-hour and 12-hour lactate clearance was higher for good neurologic outcome patients (35.3 ± 34.6% vs 6.89 ± 47.4% P = 0.01, 54.5 ± 23.7% vs 25.6 ± 43.7% P <0.01, respectively). After adjusting for potential confounding variables, the 12-hour lactate clearance still showed a statistically significant difference (P = 0.02).

Conclusion

The lactate clearance rate, and not the initial lactate level, was associated with neurological outcome in OHCA patients after therapeutic hypothermia.     

Resting energy expenditure and substrate oxidation rates correlate to temperature and outcome after cardiac arrest - a prospective observational cohort study

IntroductionTargeted temperature management improves outcome after cardiopulmonary resuscitation. Reduction of resting energy expenditure might be one mode of action. The aim of this study was to correlate resting energy expenditure and substrate oxidation rates with targeted temperature management at 33°C and outcome in patients after cardiac arrest.MethodsThis prospective, observational cohort study was performed at the department of emergency medicine and a medical intensive care unit of a university hospital. Patients after successful cardiopulmonary resuscitation undergoing targeted temperature management at 33°C for 24 hours with subsequent rewarming to 36°C and standardized sedation, analgesic and paralytic medication were included. Indirect calorimetry was performed five times within 48 h after cardiac arrest. Measurements were correlated to outcome with repeated measures ANOVA, linear and logistic regression analysis.ResultsIn 25 patients resting energy expenditure decreased 20 (18 to 27) % at 33°C compared to 36°C without differences between outcome groups (favourable vs. unfavourable: 25 (21 to 26) vs. 21 (16 to 26); P = 0.5). In contrast to protein oxidation rate (favourable vs. unfavourable: 35 (11 to 68) g/day vs. 39 (7 to 75) g/day, P = 0.8) patients with favourable outcome had a significantly higher fat oxidation rate (139 (104 to 171) g/day vs. 117 (70 to 139) g/day, P <0.05) and a significantly lower glucose oxidation rate (30 (−34 to 88) g/day vs. 77 (19 to 138) g/day; P < 0.05) as compared to patients with unfavourable neurological outcome.ConclusionsTargeted temperature management at 33°C after cardiac arrest reduces resting energy expenditure by 20% compared to 36°C. Glucose and fat oxidation rates differ significantly between patients with favourable and unfavourable neurological outcome.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00500825","term_id":"NCT00500825"}}NCT00500825. Registered 11 July 2007.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0856-2) contains supplementary material, which is available to authorized users.     

Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock

Introduction

Recent clinical studies have shown a relationship between abnormalities in peripheral perfusion and unfavorable outcome in patients with circulatory shock. Nitroglycerin is effective in restoring alterations in microcirculatory blood flow. The aim of this study was to investigate whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients.

Methods

This interventional study recruited patients who had circulatory shock and who persisted with abnormal peripheral perfusion despite normalization of global hemodynamic parameters. Nitroglycerin started at 2 mg/hour and doubled stepwise (4, 8, and 16 mg/hour) each 15 minutes until an improvement in peripheral perfusion was observed. Peripheral circulation parameters included capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen saturation (StO₂) during a reactive hyperemia test (RincStO₂). Measurements were performed before, at the maximum dose, and after cessation of nitroglycerin infusion. Data were analyzed by using linear model for repeated measurements and are presented as mean (standard error).

Results

Of the 15 patients included, four patients (27%) responded with an initial nitroglycerin dose of 2 mg/hour. In all patients, nitroglycerin infusion resulted in significant changes in CRT, Tskin-diff, and PI toward normal at the maximum dose of nitroglycerin: from 9.4 (0.6) seconds to 4.8 (0.3) seconds (P <0.05), from 3.3°C (0.7°C) to 0.7°C (0.6°C) (P <0.05), and from [log] -0.5% (0.2%) to 0.7% (0.1%) (P <0.05), respectively. Similar changes in StO₂ and RincStO₂ were observed: from 75% (3.4%) to 84% (2.7%) (P <0.05) and 1.9%/second (0.08%/second) to 2.8%/second (0.05%/second) (P <0.05), respectively. The magnitude of changes in StO₂ was more pronounced for StO₂ of less than 75%: 11% versus 4%, respectively (P <0.05).

Conclusions

Dose-dependent infusion of nitroglycerin reverted abnormal peripheral perfusion and poor tissue oxygenation in patients following circulatory shock resuscitation. Individual requirements of nitroglycerin dose to improve peripheral circulation vary between patients. A simple and fast physical examination of peripheral circulation at the bedside can be used to titrate nitroglycerin infusion.     

Platelet aggregation and clot formation in comatose survivors of cardiac arrest treated with induced hypothermia and dual platelet inhibition with aspirin and ticagrelor; a prospective observational study

Introduction

We conducted a prospective observational study in cardiac arrest survivors treated with mild induced hypothermia, evaluating different platelet function tests at hypo- and normothermia. We also investigated the relation between gastric emptying and vasodilator stimulated phosphoprotein (VASP).

Methods

Comatose survivors of out of hospital cardiac arrest were included and divided into two groups, depending on whether dual platelet inhibition with peroral ticagrelor and aspirin was given or not. The first blood samples (T1) were collected 12–24 hours after reaching target temperature (33°C) and were compared to blood samples collected 12–28 hours after reaching normothermia (37°C) (T2) within each group. All samples were analysed by Sonoclot viscoelasticity, flow cytometry based VASP and with multiple electrode aggregometry, Multiplate®; adenosine diphosphate (ADP), collagen (COL), thrombin receptor agonist peptide (TRAP) and arachidonic acid (ASPI). Sonoclot and Multiplate® instruments were set on in vivo temperatures. Gastric secretion from the nasogastric tube was measured to assess absorption of per orally administered antiplatelet drugs. Differences between T1 and T2 within each group were calculated using Wilcoxon matched pairs signed test. Significance levels were set at P <0.01.

Results

In total, 23 patients were included. In patients with dual platelet inhibition (n =14) Multiplate®-analyses showed no changes in ADP stimulated platelets. COL, TRAP and ASPI aggregations were higher at T2 compared to T1. Sonoclot-analyses showed that activated clotting time (ACT) was unchanged but both clot rate (CR) and platelet function (PF) were higher at T2 compared to T1. VASP decreased from 53 ± 28(T1) to 24 ± 22(T2), (P <0.001). The average volume of gastric secretion aspirated before T1 correlated well with VASP (T1), r =0.81 (P <0.001). In patients with no platelet inhibition, (n =9) similar changes between T1 and T2 were seen as in patients with dual platelet inhibition while VASP was unchanged.

Conclusions

We have demonstrated increased platelet aggregation and strengthened clot formation over time in out of hospital cardiac arrest patients treated with hypothermia. In patients on oral dual platelet inhibition, the effect of ticagrelor was delayed, probably due to slow gastric emptying.     

Elevation of cardiac troponin I during non-exertional heat-related illnesses in the context of a heatwave

Introduction

The prognostic value of cardiac troponin I (cTnI) in patients having a heat-related illness during a heat wave has been poorly documented.

Methods

In a post hoc analysis, we evaluated 514 patients admitted to emergency departments during the August 2003 heat wave in Paris, having a core temperature >38.5°C and who had analysis of cTnI levels. cTnI was considered as normal, moderately elevated (abnormality threshold to 1.5 ng.mL^-1), or severely elevated (>1.5 ng.mL^-1). Patients were classified according to our previously described risk score (high, intermediate, and low-risk of death).

Results

Mean age was 84 ± 12 years, mean body temperature 40.3 ± 1.2°C. cTnI was moderately elevated in 165 (32%) and severely elevated in 97 (19%) patients. One-year survival was significantly decreased in patients with moderate or severe increase in cTnI (24 and 46% vs 58%, all P < 0.05). Using logistic regression, four independent variables were associated with an elevated cTnI: previous coronary artery disease, Glasgow coma scale <12, serum creatinine >120 μmol.L^-1, and heart rate >110 bpm. Using Cox regression, only severely elevated cTnI was an independent prognostic factor (hazard ratio 1.93, 95% confidence interval 1.35 to 2.77) when risk score was taken into account. One-year survival was decreased in patients with elevated cTnI only in high risk patients (17 vs 31%, P = 0.04).

Conclusions

cTnI is frequently elevated in patients with non-exertional heat-related illnesses during a heat wave and is an independent risk factor only in high risk patients where severe increase (>1.5 ng.mL^-1) indicates severe myocardial damage.     

Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study

Introduction

Whole-body ischemia and reperfusion trigger a systemic inflammatory response. In this study, we analyzed the effect of temperature on the inflammatory response in patients treated with prolonged mild hypothermia after cardiac arrest.

Methods

Ten comatose patients with return of spontaneous circulation after pulseless electrical activity/asystole or prolonged ventricular fibrillation were treated with mild therapeutic hypothermia for 72 hours after admission to a tertiary care university hospital. At admission and at 12, 24, 36, 48, 72, 96 and 114 hours, the patients’ temperature was measured and blood samples were taken from the arterial catheter. Proinflammatory interleukin 6 (IL-6) and anti-inflammatory (IL-10) cytokines and chemokines (IL-8 and monocyte chemotactic protein 1), intercellular adhesion molecule 1 and complement activation products (C1r-C1s-C1inhibitor, C4bc, C3bPBb, C3bc and terminal complement complex) were measured. Changes over time were analyzed with the repeated measures test for nonparametric data. Dunn’s multiple comparisons test was used for comparison of individual time points.

Results

The median temperature at the start of the study was 34.3°C (33.4°C to 35.2°C) and was maintained between 32°C and 34°C for 72 hours. All patients were passively rewarmed after 72 hours, from (median (IQR)) 33.7°C (33.1°C to 33.9°C) at 72 hours to 38.0°C (37.5°C to 38.1°C) at 114 hours (P <0.001). In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming.

Conclusions

Prolonged hypothermia may blunt the inflammatory response after rewarming in patients after cardiac arrest. Complement activation was low during the whole hypothermia period, indicating that complement activation is also highly temperature-sensitive in vivo. Because inflammation is a strong mediator of secondary brain injury, a blunted proinflammatory response after rewarming may be beneficial.     

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Humoral factors released from platelets during pulmonary embolism may be the cause of several attendant cardiopulmonary abnormalities. This study examines the role of thromboxanes (Tx) after experimental embolism induced with 0.5 g/kg autologous clot in four groups of five dogs: (a) untreated embolized controls; (b) pretreatment with the Tx synthetase inhibitor, imidazole 25 mg/kg · h i.v., starting 30 min before embolization; (c) pretreatment with the cyclooxygenase inhibitor indomethacin, 5 mg/kg, 12 h per os and 1 mg/kg, 1 h i.v. before the experiment; (d) treatment with prostacyclin (PGI₂) 100 ηg/kg · min i.v. for 1 h, 1 h after embolization. Within 30 min, embolization led to increases of 6-keto-PGF_1α, the stable hydrolysis product of PGI₂, from 0.11±0.08 ηg/ml (mean±SD) to 0.33±0.10 ηg/ml (P < 0.005) and TxB₂, the stable product of TxA₂, from 0.10±0.04 ηg/ml to 0.38±0.06 ηg/ml (P < 0.001). Increases were observed in total dead space (V_D/V_T) from 0.46±0.03 to 0.61±0.08 (P < 0.025, physiologic shunting (_S/_T) from 16±4% to 38±9% (P < 0.01), pulmonary vascular resistance (PVR) from 2.27±0.59 mm Hg·min/liter to 9.21±1.90 mm Hg·min/liter (P < 0.005) and mean pulmonary arterial pressure from 14±6 mm Hg to 34±1 mm Hg (P < 0.001). Cardiac index (CI) fell from 139±11 ml/kg·min to 95±17 ml/kg·min in 4 h (P < 0.025). Imidazole pretreatment prevented a rise of TxB₂, but not 6-keto-PGF_1α; indomethacin blocked both. Both agents maintained V_D/V_T at base line and limited increases in _S/_T and PVR. CI was higher after imidazole pretreatment compared with controls (P < 0.025). Indomethacin led to intermediate levels of CI. PGI₂ lowered TxB₂ (P < 0.025), V_D/V_T (P < 0.025), _S/_T (P < 0.025) and PVR (P < 0.05) within 30 min. During PGI₂ infusion, CI was higher than controls. Concentrations of TxB₂ correlated with V_D/V_T, r = 0.79 and _S/_T, r = 0.69 (P < 0.001). Treatment of three dogs with the imidazole derivative ketoconazole, 10 mg/kg IV, 30 min after 0.75 g/kg autologous clot resulted in a lowering of physiologic dead space, but no other improvement of cardiopulmonary function. These results show that a number of cardiopulmonary abnormalities induced by pulmonary embolism are related directly or indirectly to platelet secretions and that V_D/V_T is closely allied to TxA₂ levels.     

Postoperative intubation time is associated with acute kidney injury in cardiac surgical patients

Introduction

Acute kidney injury (AKI) is a frequent complication after cardiac surgery and is associated with a poor prognosis. Mechanical ventilation is an important risk factor for developing AKI in critically ill patients. Ventilation with high tidal volumes has been associated with postoperative organ dysfunction in cardiac surgical patients. No data are available about the effects of the duration of postoperative respiratory support in the immediate postoperative period on the incidence of AKI in patients after cardiac surgery.

Method

We performed a secondary analysis of 584 elective cardiac surgical patients enrolled in an observational trial on the association between preoperative cerebral oxygen saturation and postoperative organ dysfunction and analyzed the incidence of AKI in patients with different times to extubation. The latter variable was graded in 4 h intervals (if below 16 h) or equal to or greater than 16 h. AKI was staged according to the AKI Network criteria.

Results

Overall, 165 (28.3%) patients developed AKI (any stage), 43 (7.4%) patients needed renal replacement therapy. Patients developing AKI had a significantly (P <0.001) lower renal perfusion pressure (RPP) in the first 8 hours after surgery (57.4 mmHg (95% CI: 56.0 to 59.0 mmHg)) than patients with a postoperatively preserved renal function (60.5 mmHg ((95% CI: 59.9 to 61.4 mmHg). The rate of AKI increased from 17.0% in patients extubated within 4 h postoperatively to 62.3% in patients ventilated for more than 16 h (P <0.001). Multivariate logistic regression analysis of variables significantly associated with AKI in the univariate analysis revealed that the time to the first extubation (OR: 1.024/hour, 95% CI: 1.011 to 1.044/hour; P <0.001) and RPP (OR: 0.963/mmHg; 95% CI: 0.934 to 0.992; P <0.001) were independently associated with AKI.

Conclusion

Without taking into account potentially unmeasured confounders, these findings are suggestive that the duration of postoperative positive pressure ventilation is an important and previously unrecognized risk factor for AKI in cardiac surgical patients, independent from low RPP as an established AKI trigger, and that even a moderate delay of extubation increases AKI risk. If replicated independently, these findings may have relevant implications for clinical care and for further studies aiming at the prevention of cardiac surgery associated AKI.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0547-4) contains supplementary material, which is available to authorized users.     

Effects of thoracic epidural anesthesia on survival and microcirculation in severe acute pancreatitis: a randomized experimental trial

Introduction

Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study.

Methods

In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO₂) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination.

Results

Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05).

Conclusions

TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis.     

Thyroid hormone alterations in trauma patients requiring massive transfusion: An observational study

BACKGROUND:

Although non-thyroidal illness syndrome (NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine (fT3) levels in trauma patients requiring massive transfusion have not been reported.

METHODS:

A prospective observational study comparing 2 groups of trauma patients was conducted. Group M comprised trauma patients requiring massive transfusions (>10 units of packed red blood cells) within 24 hours of emergency admission. Group C comprised patients with an injury severity score >9 but not requiring massive transfusions. Levels of fT3, free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated on admission and on days 1, 2, and 7 after admission. The clinical backgrounds and variables measured including total transfusion amounts were compared and the inter-group prognosis was evaluated. Results are presented as mean±standard deviation.

RESULTS:

Nineteen patients were enrolled in each group. In both groups, 32 were men, and the mean age was 50±24 years. In group C one patient died from respiratory failure. The initial fT3 levels in group M (1.95±0.37 pg/mL) were significantly lower than those in group C (2.49±0.72 pg/mL; P<0.01) and remained low until 1 week after admission. Initial inter-group fT4 and TSH levels were not significantly different. TSH levels at 1 week (1.99±1.64 µIU/mL) were higher than at admission (1.48±0.5 µIU/mL) in group C (P<0.05).

CONCLUSION:

Typical NTIS was observed in trauma patients requiring massive transfusions. When initial resuscitation achieved circulatory stabilization, prognosis was not strongly associated with NTIS.KEY WORDS: Non-thyroidal illness syndrome, Massive transfusion, Trauma, Free triiodothyronine, Thyroid hormone