Red blood cell distribution width and Charlson comorbidity index help to identify frail polytraumatized patients : Experiences from a level I trauma center.

INTRODUCTION: Little is known about the potential impact of the red blood cell distribution width (RDW) and pre-existing comorbidities on the late-phase survival of polytraumatized patients. METHODS: A total of 173 polytraumatized patients were included retrospectively in this cohort study in a level I trauma center from January 2012 to December 2015. The Charlson comorbidity index (CCI) scores and RDW values were evaluated. RESULTS: Out of all polytraumatized patients (n = 173), 72.8% (n = 126) were male, the mean ISS was 31.7 points (range 17-75) and the mean age was 45.1 years (range 18-93 years). Significantly higher RDW values (13.90 vs. 13.37; p = 0.006) and higher CCI scores (3.38 vs. 0.49; p < 0.001) were seen in elderly polytraumatized patients (age > 55 years). RDW values > 13.75% (p = 0.033) and CCI scores > 2 points (p = 0.001) were found to have a significant influence on the late-phase survival of polytraumatized patients. Age > 55 years (p = 0.009, HR 0.312; 95% confidence interval (CI) 0.130-0.749) and the presence of severe traumatic brain injury (TBI) (p = 0.007; HR 0.185; 95% CI 0.054-0.635) remained as independent prognostic factors on the late-phase survival after multivariate analysis. CONCLUSION: Even younger elderly polytraumatized patients (> 55 years of age) showed significant higher RDW values and higher CCI scores. In addition to the presence of severe TBI and age > 55 years, RDW value > 13.75% on admission and CCI score > 2 might help to identify the "younger" frail polytraumatized patient at risk.

Platelet hyperfunction is decreased by additional aspirin loading in patients presenting with myocardial infarction on daily aspirin therapy.

OBJECTIVE: Currently 162-325 mg aspirin is recommended for the treatment of acute coronary syndrome. We tested the effect of an additional loading dose of 250 mg aspirin at the onset of acute coronary syndrome in patients who were already on chronic therapy with 100 mg aspirin. DESIGN: This was a prospective trial in patients presenting with symptoms suggestive of acute coronary syndrome that included a randomized, double-blind, placebo-controlled trial subgroup. SETTING: An emergency department in a tertiary care center. PATIENTS: Consecutive patients with symptoms suggestive of acute coronary syndrome were enrolled, including a cohort already on chronic aspirin therapy. INTERVENTIONS: Patients received an intravenous infusion of 250 mg aspirin. MEASUREMENTS AND MAIN RESULTS: Platelet function was measured with a platelet function analyzer in 234 patients before and after aspirin infusion. Aspirin infusion prolonged collagen epinephrine closure times in almost all patients. Aspirin infusion further lowered thromboxane B(2) levels in patients with acute coronary syndrome who were on chronic aspirin therapy before admission. Concomitantly, collagen epinephrine closure times increased by 22% from 223 secs (95% confidence interval, 192-255 secs) before to 273 secs (95% confidence interval, 252-294 secs) after aspirin infusion (p < .01). Eleven patients with ST-elevation myocardial infarction on daily aspirin therapy (53%) displayed platelet hyperfunction (collagen epinephrine closure times <193 secs). Additional aspirin infusion further decreased platelet function in these patients with ST-elevation myocardial infarction (30% prolongation of collagen epinephrine closure times; p < .01), and only two patients with ST-elevation myocardial infarction still displayed platelet hyperfunction (p = .02). CONCLUSION: Aspirin loading in the emergency room further reduced thromboxane B(2) levels and further inhibited platelet function in many patients with acute coronary syndrome already on 100 mg aspirin.

Cold aortic flush and chest compressions enable good neurologic outcome after 15 mins of ventricular fibrillation in cardiac arrest in pigs.

OBJECTIVE: The induction of deep cerebral hypothermia via ice-cold saline aortic flush during prolonged ventricular fibrillation cardiac arrest, followed by hypothermic stasis and delayed resuscitation (emergency preservation and resuscitation), improved neurologic outcome after cardiac arrest in pigs, as compared to conventional resuscitation. We hypothesized that emergency preservation and resuscitation with chest compressions would further improve outcome in the same model. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: : Twenty-four female, large, white breed pigs (27-37 kg). INTERVENTIONS: Fifteen minutes of ventricular fibrillation cardiac arrest were followed by 20 mins of resuscitation with chest compressions (control, n = 8), deep cerebral hypothermia via 200 mL/kg 4 degrees C saline aortic flush and hypothermic stasis (emergency preservation and resuscitation, n = 8), and emergency preservation and resuscitation combined with chest compressions (emergency preservation and resuscitation plus chest compressions, n = 8). At 35 mins after cardiac arrest, cardiopulmonary bypass was initiated, followed by defibrillation. Mild hypothermia was continued for 20 hrs. Pigs were evaluated after 9 days using a neurologic deficit (neurologic deficit score: 100% = brain dead; 0%-10% = normal) and an overall performance category score (overall performance category score: 1 = normal; 2 = slightly handicapped; 3 = severely handicapped; 4 = comatose; 5 = dead/brain dead). MEASUREMENTS AND MAIN RESULTS: Brain temperature decreased from 38.5 degrees C to 15.3 degrees C +/- 3.3 degrees C in the emergency preservation and resuscitation group, and to 11.3 degrees C +/- 1.2 degrees C in the emergency preservation and resuscitation plus chest compressions group. In the control group, restoration of spontaneous circulation was achieved in four out of eight pigs, and one survived to 9 days. In the emergency preservation and resuscitation group, restoration of spontaneous circulation was achieved in seven out of eight pigs and five survived; in the emergency preservation and resuscitation plus chest compressions group, all had restoration of spontaneous circulation and seven survived (restoration of spontaneous circulation, p = .08). Neurologic outcome for (median and interquartile range) the control group included overall performance category score of 3, neurologic deficit score of 45%; for the emergency preservation and resuscitation group, overall performance category score was 3 (2-5) and neurologic deficit score was 45% (36; 50) and in the emergency preservation and resuscitation plus chest compressions group, overall performance category score was 2 (1-3) and neurologic deficit score was 13% (5; 21) (overall performance category score, p = .04; neurologic deficit score emergency preservation and resuscitation vs. emergency preservation and resuscitation plus chest compressions, p = .003). CONCLUSIONS: Emergency preservation and resuscitation by deep cerebral hypothermia combined with chest compressions during prolonged cardiac arrest in pigs are feasible and improve neurologic outcome.

Pronounced platelet hyperfunction in patients with cardiac arrest achieving restoration of spontaneous circulation.

OBJECTIVE: Markers of platelet activation are increased in patients undergoing cardiopulmonary resuscitation. Hyperfunctional platelets may contribute to impairment of microcirculatory function and overall poor outcome despite restoration of spontaneous circulation (ROSC). Patients with myocardial infarction have hyperfunctional platelets, which predict the degree of myocardial necrosis. Thus, we hypothesized that platelets may be even more activated in patients whose myocardial infarction leads to cardiac arrest and compared them with patients whose cardiac arrest was due to a noncardiac origin. DESIGN: Prospective observational study. SETTING: Emergency department of a tertiary care hospital. PATIENTS: One hundred four patients with witnessed cardiac arrest who achieved ROSC. INTERVENTIONS: Blood sampling. MEASUREMENTS AND MAIN RESULTS: We assessed collagen adenosine diphosphate closure time with the platelet function analyzer-100, and measured plasma levels of von Willebrand factor: ristocetin cofactor activity levels by turbidometry. Independent physicians diagnosed the origin of cardiac arrest. The majority of cardiac arrests were caused by myocardial ischemia. Invariably, collagen adenosine diphosphate closure time values (55 seconds; 95% confidence interval: 52-58 seconds) were much shorter in these patients compared with patients with other causes of cardiac arrest (110 seconds; 95% confidence interval: 84-135 seconds, p < 0.001). von Willebrand factor: ristocetin cofactor activity plasma levels were more than three-fold above normal values in both groups. CONCLUSIONS: Patients with myocardial ischemia-triggered cardiac arrest had the highest degree of platelet hyperfunction under high shear rates, which was not solely due to increased von Willebrand factor. Future trials are necessary to clarify whether rapid, more aggressive antiplatelet therapy improves outcome after cardiac arrest.

Correction to: Non-vitamin K antagonist oral anticoagulants in patients with an increased risk of bleeding.

Correction to: Wien Klin Wochenschr 2018 https://doi.org/10.1007/s00508-018-1381-5 Unfortunately, the original version of this article contained two mistakes.The text passage "It should be mentioned here that in the case of apixaban, dose adjustment is not based on GFR. A lower dosage of apixaban ….

Rapid non-invasive external cooling to induce mild therapeutic hypothermia in adult human-sized swine.

AIM OF THE STUDY: Mild therapeutic hypothermia is a promising new therapy for patients resuscitated from cardiac arrest. Early and fast induction of hypothermia seems to be crucial for best results. The aim of the study was to investigate the feasibility and safety of a new surface cooling method using cold metal plates. SUBJECTS AND METHODS: Twelve adult human-sized swine (79+/-9 kg) were cooled from 38 to 33 degrees C brain temperature. The skin surface was covered with -20 degrees C metal plates (M), as compared to ice packs, alcohol rubs, and fans used in a control group (C). Each method was tested during spontaneous circulation and, after re-warming, during cardiac arrest. Temperatures were recorded continuously. Data are given as mean+/-standard deviation or as median (interquartile range), if not normally distributed. Comparisons between the treatment groups were performed with the independent samples t-test, or the Mann-Whitney rank-sum test. RESULTS: During spontaneous circulation, cooling rates were 9.3+/-1.4 degrees C/h (M), and 6.1+/-1.4 degrees C/h (C) (p=0.003); no skin lesions were observed. During cardiac arrest, cooling rates were 4.1 degrees C/h (1.8-4.8) (M), and 3.7 degrees C/h (3.1-5.3) (C) (p=0.9); no skin lesions were observed. CONCLUSION: Cooling with cold metal plates was an effective method for rapid induction of mild therapeutic hypothermia in adult human-sized swine during spontaneous circulation, without any signs of skin damage. This new surface-cooling device, independent of energy supply during use, should be further investigated.

Non-vitamin K antagonist oral anticoagulants in patients with an increased risk of bleeding.

The non-vitamin K antagonist oral anticoagulants (NOACs) have considerably changed clinical practice and are increasingly being used as an alternative to vitamin K antagonists (VKAs) for 3 main reasons: 1) an improved benefit-risk ratio (in particular lower rates of intracranial bleeding), 2) a more predictable effect without the need for routine monitoring, and 3) fewer food and drug interactions compared with VKAs. Currently, there are four NOACs available: the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, and the thrombin inhibitor dabigatran. This consensus paper reviews the properties and usage of NOACs in a number of high-risk patient populations, such as patients with chronic kidney disease, patients ≥80 years of age and others and provides guidance for the use of NOACs in patients at risk of bleeding.

Can brain natriuretic peptide predict outcome after cardiac arrest? An observational study.

BACKGROUND: No accurate, independent biomarker has been identified that could reliably predict neurological outcome early after cardiac arrest. We speculated that brain natriuretic peptide (BNP) measured at hospital admission may predict patient outcome. METHODS: BNP-levels were measured in 155 comatose cardiac arrest survivors (108 male, 58 years [IQR 49-68]) (median time to ROSC 11min; IQR 20-30) during a 6-year study period. Cardiovascular co-morbidities and resuscitation history were assessed according to the Utstein-style and patients were followed for 6-month neurological outcome measured by cerebral performance category (CPC) and survival. RESULTS: Seventy patients (45%) suffered from unfavourable neurological outcome and 79 deaths (51%) occurred during the first 6 months. BNP was significantly associated with an adverse neurological outcome and mortality, independent of the prearrest health condition and cardiac arrest characteristics (median 60 pg/ml; IQR 10-230). Adjusted odds ratios for poor neurological outcome at 6 months were 1.14 (95% CI 0.51-2.53), 1.76 (95% CI 0.80-3.88) and 2.25 (95% CI 1.05-4.81), for increasing quartiles of BNP as compared to the lowest quartile. Adjusted odds ratios for mortality until 6 months were 1.09 (95% CI 0.35-3.40), 2.81 (0.80-9.90) and 4.7 (1.27-17.35) compared to the lowest quartile, respectively. CONCLUSION: Brain natriuretic peptide levels on admission predict neurological outcome at 6 months and survival after cardiac arrest.

Continuous versus intermittent neuromuscular blockade in patients during targeted temperature management after resuscitation from cardiac arrest-A randomized, double blinded, double dummy, clinical trial.

AIM OF THE STUDY: Current guidelines recommend targeted temperature management to improve neurological outcome after cardiac arrest. Evidence regarding an ideal sedative/analgesic regimen including skeletal muscle paralysis is limited. METHODS: Patients were randomized to either a continuous administration of rocuronium (continuous-NMB-group) or to a continuous administration of saline supplemented by rocuronium bolus administration if demanded (bolus-NMB-group). The primary outcome was the number of shivering episodes. Secondary outcomes included survival and neurological status one year after cardiac arrest, time to awakening, length of stay as well as required cumulative dose of rocuronium, midazolam and fentanyl. RESULTS: Sixty-three patients (32 continuous-NMB-group; 31 bolus-NMB-group) were enrolled. Differences in baseline characteristics were not significant. Shivering episodes were detected in 94% of the patients in the bolus-NMB-group compared to 25% of the patients receiving continuous rocuronium infusion (p<0.01). The continuous-NMB-group received significant lower doses of midazolam (4.3±0.8mg/kg vs. 5.1±0.9mg/kg, p<0.01) and fentanyl (62±14µg/kg vs. 71±7µg/kg, p<0.01), but higher cumulative doses of rocuronium (7.8±1.8mg/kg vs. 2.3±1.6mg/kg, p<0.01). Earlier awakening (2 [IQR 2;3] vs. 4 [IQR 2;7.5] days, p=0.04) and decreased length of stay at the ICU (6 [IQR 3;5.9] vs. 10 [IQR 5;15] days, p=0.03) were observed in the continuous-NMB-group. There were no significant differences in survival and quality of life 12 months after cardiac arrest. CONCLUSIONS: Continuous neuromuscular blockade during the first day after resuscitation reduced shivering, midazolam and fentanyl requirement, time to awakening and discharge from intensive care unit. There were no differences in overall survival, cooling rate and time to target temperature.

Platelet function predicts myocardial damage in patients with acute myocardial infarction.

BACKGROUND: Platelet activation is a hallmark of acute coronary syndromes. Numerous lines of evidence suggest a mechanistic link between von Willebrand factor or platelet hyperfunction and myocardial damage in patients with acute coronary syndromes. Thus, we assessed whether platelet function under high shear rates (collagen adenosine diphosphate closure times [CADP-CTs]) measured with the platelet function analyzer (PFA-100) may be enhanced in patients with myocardial infarction (MI) and whether it may predict the extent of myocardial damage as measured by creatine kinase (CK-MB) or troponin T (TnT) levels. METHODS AND RESULTS: Patients with acute chest pain or symptoms suggestive of acute coronary syndromes (n=216) were prospectively examined at an emergency department. CADP-CT was significantly shorter in patients with MI, particularly in those with an ST-segment-elevation MI (STEMI) compared with the other patient groups (unstable angina, stable coronary artery disease, or controls). Furthermore, CADP-CT and collagen epinephrine-CT at presentation were independent predictors of myocardial damage as measured by CK-MB or TnT. Patients with MI whose CADP-CT values fell in the first quartile had 3-fold higher CK-MB and TnT levels than those in the fourth quartile. CONCLUSIONS: Patients with STEMI have significantly enhanced platelet function when measured under high shear rates. CADP-CT is an independent predictor of the severity of MI, as measured by markers of cardiac necrosis. Measurement of platelet function with the PFA-100 may help in the risk stratification of patients presenting with MI.

Activation of calcium-dependent calmodulin by calcium(II)3(3,5-diisopropylsalicylate)6(H2O)6 decreases thrombin receptor activating peptide-induced P-selectin expression.

We examined the influence of 3,5-diisopropylsalicylic acid (3,5-DIPS) and calcium(II)3 (3,5-diisopropylsalicylate)6 (H2 O)6 [Ca(II)3 (3,5-DIPS)6 ], a new activator of calcium-dependent calmodulin-triggered nitric oxide synthase, on thrombin-induced platelet P-selectin expression. Citrated whole blood samples were incubated with either ethanol vehicle, 3,5-DIPS, or Ca(II)3 (3,5-DIPS)6. These whole blood samples were also co-incubated with thrombin receptor activating peptide (TRAP) or adenosine diphosphate (ADP), to up-regulate P-selectin (CD62P) on platelets. Both TRAP and ADP up-regulated P-selectin on platelets compared with platelets in whole blood samples that were not incubated with either platelet activator. Co-incubation of whole blood samples with TRAP, ADP together with 3,5-DIPS, or Ca(II)3 (3,5-DIPS)6 revealed that Ca(II)3 (3,5-DIPS)6 caused a decrease in platelet P-selectin expression for TRAP, ADP, and no-activator co-incubated samples of whole blood. Incubation of platelets with 3,5-DIPS also caused a decrease in ADP-induced up-regulation of P-selectin but failed to affect TRAP or no-activator-treated platelets. Incubation of whole blood with Ca(II)3 (3,5-DIPS)6 induced some hemolysis. We found that hemolysis increases basal P-selectin expression on platelets. We therefore conclude that Ca(II)3 (3,5-DIPS)6 decreased not only basal, but also hemolysis-induced P-selectin expression on platelets. In contrast, incubation of haemolysed whole blood with SIN-1 (standard nitric oxide-releasing drug) had no effect on P-selectin expression. In summary, Ca(II)3 (3,5-DIPS)6, a new calmodulin-dependent nitric oxide synthase activator, decreases P-selectin expression of human platelets in response to thrombin receptor activation. Improved calcium-dependent calmodulin activators may become useful drugs for the treatment of disorders associated with platelet activation, and P-selectin may decrease expression due to hemolysis.

Severe accidental hypothermia with or without hemodynamic instability: rewarming without the use of extracorporeal circulation.

BACKGROUND: The optimal rewarming technique for patients in deep accidental hypothermia with core temperatures below 28 degrees C is not established. Several authors believe that extracorporeal rewarming is essential, especially for patients with hemodynamic instability. Others believe that invasive rewarming ought to be reserved for patients in cardiac arrest. We describe our experience with a strictly conservative technique without the use of invasive rewarming devices in patients with severe accidental hypothermia and a sustained perfusion rhythm. METHODS: A cohort study extending from 1991 to 2000, including all patients received at the emergency department of the University Hospital of Vienna with severe hypothermia, a core temperature of maximum 28 degrees C and no preclinical cardiac arrest. RESULTS: 36 patients with deep hypothermia were included in the study. Their core temperatures ranged from 20.2 degrees C to 28 degrees C; the median temperature was 25.75 degrees C (25th and 75th percentile, 24.2/27.3). Fourteen patients were intoxicated and their multimorbidity was high. All of 19 patients with stable hemodynamics and 14 of 17 patients with unstable hemodynamics were successfully rewarmed to normothermia with warmed infusions, inhalation rewarming and forced air rewarming. The rewarming process took 9.5 hours (8/10.5) and required a volume load of 4820 ml (2735/5770). The rewarming rate was 1.09 degrees C per hour (0.94/1.25). Although 92% of the patients were successfully rewarmed to normothermia, in-hospital mortality was 42%, but was largely related to comorbidity. DISCUSSION: A conservative approach is highly successful in achieving normothermia in patients with deep hypothermia with or without stable hemodynamics. In-hospital mortality of severe accidental hypothermia in urban conditions is high; comorbidity might play a major role. The influence of the rewarming strategy on late in-hospital mortality remains unclear.

Lipid-induced insulin resistance is not mediated by impaired transcapillary transport of insulin and glucose in humans.

Increased lipid availability reduces insulin-stimulated glucose disposal in skeletal muscle, which is generally explained by fatty acid-mediated inhibition of insulin signaling. It remains unclear whether lipids also impair transcapillary transport of insulin and glucose, which could become rate controlling for glucose disposal. We hypothesized that lipid-induced insulin resistance is induced by inhibiting myocellular glucose uptake and not by interfering with the delivery of insulin or glucose. We measured changes in interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides plus heparin or glycerol during physiologic and supraphysiologic hyperinsulinemia, by combining microdialysis with oral glucose tolerance tests and euglycemic-hyperinsulinemic clamps. Lipid infusion reduced insulin-stimulated glucose disposal by ~70% (P < 0.05) during clamps and dynamic insulin sensitivity by ~12% (P < 0.05) during oral glucose loading. Dialysate insulin and glucose levels were unchanged or even transiently higher (P < 0.05) during lipid than during glycerol infusion, whereas regional blood flow remained unchanged. These results demonstrate that short-term elevation of free fatty acids (FFAs) induces insulin resistance, which in skeletal muscle occurs primarily at the cellular level, without impairment of local perfusion or transcapillary transport of insulin and glucose. Thus, vascular effects of FFAs are not rate controlling for muscle insulin-stimulated glucose disposal.

Emergency preservation and resuscitation improve survival after 15 minutes of normovolemic cardiac arrest in pigs.

OBJECTIVE: Outcome after prolonged normovolemic cardiac arrest is poor, and new resuscitation strategies have to be found. We hypothesized that the induction of deep hypothermia for emergency preservation and resuscitation (EPR) during prolonged cardiac arrest, before the start of reperfusion, will mitigate the deleterious cascades leading to neuronal death and will thus improve outcome. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: Thirteen pigs, Large White breed (27-37 kg). INTERVENTIONS: After 15 mins of ventricular fibrillation, pigs were subjected to 1) EPR (n = 6), 20 mins of hypothermic stasis induced with a cold saline aortic flush; or 2) 20 mins of conventional resuscitation (n = 7). Then cardiopulmonary bypass was initiated in both groups, followed by defibrillation. Controlled ventilation and mild hypothermia were continued for 20 hrs; survival was for 9 days. For neurologic evaluation, neurologic deficit score (100% = brain dead, 0-10% = normal), overall performance category (1 = normal, 5 = dead or brain dead), and brain histologic damage score were used. MEASUREMENTS AND MAIN RESULTS: In the EPR group, brain temperature decreased from 38.5 degrees C +/- 0.2 degrees C to 16.7 degrees C +/- 2.5 degrees C within 235 +/- 27 secs. Five animals achieved restoration of spontaneous circulation and survived to 9 days: two pigs with overall performance category 2 and three pigs with overall performance category 3. Their neurologic deficit score was 45% (interquartile range 35, 50) and histologic damage score was 142 (interquartile range 109, 159). In the control group, four pigs achieved restoration of spontaneous circulation: one survived to 9 days with overall performance category 3, neurologic deficit score 45%, and histologic damage score 226 (restoration of spontaneous circulation, p = .6; survival, p = .03; overall performance category, p = .02). CONCLUSIONS: EPR is feasible in an experimental pig model and improves survival after prolonged cardiac arrest in pigs. Further experimental studies are needed before this concept can be brought into clinical practice.

Rapid induction of cerebral hypothermia by aortic flush during normovolemic cardiac arrest in pigs.

OBJECTIVE: Induction of deep cerebral hypothermia before reperfusion might improve neurologic outcome after cardiac arrest. We hypothesized that an aortic flush with cold saline during cardiac arrest is able to induce deep cerebral hypothermia and that the cooling efficiency can be enhanced by a) increasing the arteriovenous pressure gradient during the flush with vasopressin; b) improving the cerebral microcirculation during the flush with the thrombolytic agent alteplase; and c) increasing the arteriovenous pressure gradient further with venting the right heart by draining blood during the flush. DESIGN: Prospective randomized experimental study. SETTING: University research laboratory. SUBJECTS: Twenty-four pigs Large White breed (31-42 kg). INTERVENTIONS: After 10 mins of ventricular fibrillation, pigs received an aortic flush (100 mL/kg, 4 degrees C, flow rate 35 mL/kg/min) into the descending aorta via a balloon catheter. The animals were subjected randomly to either an aortic flush with saline, saline plus vasopressin 1.2 IU/kg, saline plus alteplase 1 mg/kg, saline plus a combination of vasopressin 1.2 IU/kg and alteplase 1 mg/kg, or saline plus vasopressin 1.2 IU/kg and venting the right heart. Arterial and venous pressures and brain temperatures were recorded for an observation time of 10 mins after flush. MEASUREMENTS AND MAIN RESULTS: A sufficient arteriovenous pressure gradient and deep cerebral hypothermia were only achieved with a flush containing vasopressin (brain temperature 16.1+/-1.3 degrees C in the vasopressin group vs. 35.4+/-1.5 degrees C in the saline group, p<.001); combining vasopressin with alteplase, or venting the right heart, did not further enhance the cooling efficiency of the flush. CONCLUSIONS: A cold saline aortic flush with vasopressin rapidly decreases brain temperature during prolonged normovolemic cardiac arrest in pigs. Whether deep cerebral hypothermia induced before reperfusion can improve neurologic outcome after cardiac arrest needs further investigation in large animal outcome studies.

Target site penetration of fosfomycin in critically ill patients.

OBJECTIVE: The present study was undertaken to investigate the target site penetration properties of fosfomycin, an antibiotic particularly suitable for treatment of soft tissue infections (STIs) in critically ill patients. METHODS AND RESULTS: The study population included nine patients with sepsis. Penetration of fosfomycin into the interstitial space fluid of skeletal muscle was measured using the microdialysis technique, following a single intravenous administration of 8.0 g of fosfomycin to patients. The median (range) fosfomycin area under the concentration versus time profile for plasma and skeletal muscle were 673 (459-1108) and 477 (226-860) mg x h/L (P < 0.011), respectively. Interstitial maximum concentrations were lower than plasma values (P < 0.029). Median fosfomycin concentrations in the interstitium and plasma exceeded 70 mg/L throughout the observation period of 4 h and covered MICs for Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa. Simulation of bacterial growth inhibition of S. pyogenes, based on tissue concentration data, confirmed the bactericidal properties of fosfomycin described in previous studies. CONCLUSION: Fosfomycin concentrations in muscle interstitium and plasma exceeded the MICs for a range of clinically relevant pathogens in critically ill patients. Thus, fosfomycin exhibits a tissue pharmacokinetic profile, which appears to offer an alternative to other broad-spectrum antibiotics in intensive care patients suffering from STI.

Closed-chest microdialysis to measure antibiotic penetration into human lung tissue.

The majority of bacterial lung infections are localized to the interstitial space fluid, which is therefore an important target site for antimicrobial chemotherapy. Direct measurement of interstitial concentrations of antimicrobial agents in human lung tissue would allow for a more informed approach to appropriate dosing of antimicrobial agents, but until now this was beyond technical reach. In this exploratory pharmacokinetic study, we measured the time versus concentration profile of cefpirome after a single intravenous dose administration of 2 g in the lung interstitial fluid by flexible microdialysis catheters, which were implanted during lung surgery for pulmonary tumors in five patients. Cefpirome concentrations in lung interstitial fluid were 66% of corresponding plasma values within the first 240 min, and exceeded minimal inhibitory concentrations of most relevant bacteria. The experimental procedure was well tolerated by the patients and no adverse events were observed. The present study provides evidence for the first time that closed chest microdialysis of the human lung is a feasible and safe method to measure lung concentrations in patients in vivo. The present data also corroborate the use of cefpirome as a valuable agent in the treatment of lung infections with most extracellular bacteria.