Airway management may influence postoperative ventilation need in preterm infants after laser eye treatment.

BACKGROUND: Retinopathy of prematurity is treated with laser photocoagulation under general anaesthesia with intubation using endotracheal tube (ETT), which carries a risk for postoperative mechanical ventilation (MV). Laryngeal mask airway (LMA) may provide a safe alternative. We assessed the need for postoperative MV in preterm infants who received LMA versus ETT. METHODS: In this single-centre, retrospective cohort study, preterm infants who underwent laser photocoagulation between 2014-2021 were enroled. For airway management, patients received either LMA (n = 224) or ETT (n = 47). The outcome was the rate of postoperative MV. RESULTS: Patients' age were 37 [35;39] weeks of postmenstrual age, median bodyweight of Group LMA was higher than Group ETT's (2110 [1800;2780] g versus 1350 [1230;1610] g, respectively, p < 0.0001). After laser photocoagulation, 8% of Group LMA and 74% of Group ETT left the operating theatre requiring MV. Multiple logistic regression revealed that the use of LMA and every 100 g increase in bodyweight significantly decreased the odds of mechanical ventilation (OR 0.21 [95% CI 0.07-0.60], and 0.73 [95% CI 0.63-0.84], respectively). Propensity score matching confirmed that LMA decreased the odds of postoperative MV (OR 0.30 [95% CI 0.11-0.70]). CONCLUSION: The use of LMA is associated with a reduced need for postoperative MV. IMPACT: Using laryngeal mask airway instead of endotracheal tube for airway management in preterm infants undergoing general anaesthesia for laser photocoagulation for treating retinopathy of prematurity could significantly decrease the postoperative need for mechanical ventilation. According to our current understanding, this has been the largest study investigating the effect of laryngeal mask airway during general anaesthesia in preterm infants. Our study suggests that the use of laryngeal mask airway is a viable alternative to intubation in the vulnerable population of preterm infants in need of laser treatment.

[Pediatric cardiopulmonary resuscitation]. / Gyermekek újraélesztése.

Our aim is to summarize the new European Resuscitation Council (ERC) 2021 guidelines on paediatric life support. In children, exhaustion of compensatory mechanisms in respiratory or circulatory failure leads to cardiac arrest. Recognition and treatment of children in critical condition are the most important element of its prevention. With the ABCDE approach, life-threatening problems can be identified and treated using simple interventions (bag-mask ventilation, intraosseous access, fluid bolus, etc.). Important new recommendations: 4-hand ventilation during bag-mask ventilation, target saturation of 94-98% during oxygen therapy, and fluid bolus of 10 ml/kg. In pediatric basic life support, if there is no normal breathing after 5 initial rescue breaths in absence of signs of life, chest compression should be initiated immediately using primarily two-thumb encircling method for infants. Recommended rate is 100-120/min, ratio of compression to ventilation is 15 : 2. Pediatric advanced life support is a teamwork. The structure of the algorithm is unchanged, high-quality chest compression is still a paramount. Recognition and treatment of potential reversible causes (4H-4T) and the decisive role of focused ultrasound are emphasized. New features: recommendation of 4-hand technique bag-mask ventilation, role of capnography, and age-dependent ventilatory rate in the case of continuous chest compression after endotracheal intubation. Drug therapy is unchanged, the fastest way to administer adrenaline during resuscitation is via intraosseous access. Treatment after return of spontaneous circulation decisively influences neurological outcome. Patient care is further based on the ABCDE scheme. Important goals are maintaining normoxia, normocapnia, avoiding hypotension, hypoglycemia, fever and use of targeted temperature management. Orv Hetil. 2023; 164(12): 463-473.

Effect of an educational intervention on compliance with care bundle items to prevent ventilator-associated pneumonia.

OBJECTIVES: We aimed to evaluate the effectiveness of our ventilator-associated pneumonia prevention bundle implemented by education of the nursing staff, and to describe the tendency of knowledge retention. RESEARCH METHODOLOGY: A prospective, before-and-after study was performed. The ventilator-associated pneumonia prevention bundle was implemented through a single educational intervention of the nursing staff. The risk of ventilator-associated pneumonia over time was estimated using a Cox proportional cause-specific hazard model. Compliance to preventive measures was assessed at three time-points: before education, at three months and 12 months after education. SETTING: A 29-bed mixed medical-surgical intensive care unit. MAIN OUTCOME MEASURES: Ventilator-associate pneumonia incidence densities, the risk of ventilator-associated pneumonia, and compliance to preventive measures in the pre-implementation and post-implementation periods. RESULTS: We analyzed the data of 251 patients. The incidence density of pneumonia decreased from 29.3/1000 to 15.3/1000 ventilator-days after the implementation of the prevention program. Patients in the post-implementation period had significantly lower risk to develop pneumonia (hazard ratio 0.34, 95 % confidence interval 0.19-0.61, p = 0.001). At 3 months of implementation, a significant improvement was detected to all the individual bundle components. Complete compliance increased from 16.2 % to 62.2 % (p < 0.001). Compliance with bundle components decreased to baseline levels after 12 months of implementation apart from head-of-bed elevation. CONCLUSION: This study supports existing evidence that educational interventions improve compliance. The gained knowledge was well translated into clinical practice reflected by the decreasing ventilator-associated pneumonia rate. It may be assumed that a refresher educational session within 12 months after implementation is needed.

MICy: a Novel Flow Cytometric Method for Rapid Determination of Minimal Inhibitory Concentration.

Early initiated adequate antibiotic treatment is essential in intensive care. Shortening the length of antibiotic susceptibility testing (AST) can accelerate clinical decision-making. Our objective was to develop a simple flow cytometry (FC)-based AST that produces reliable results within a few hours. We developed a FC-based AST protocol (MICy) and tested it on six different bacteria strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis) in Mueller-Hinton and Luria-Bertani broth. We monitored the bacterial growth by FC to define the optimal time of AST. All bacteria were tested against 12 antibiotics and the MIC values were compared to microdilution used as reference method. McNemar and Fleiss' kappa inter-observer tests were performed to analyze the bias between the two methods. Susceptibility profiles of the two methods were also compared. We found that FC is able to detect the bacterial growth after 4-h incubation. The point-by-point comparison of MICy and microdilution resulted in exact match above 87% (2642/3024) of all measurements. The MIC values obtained by MICy and microdilution agreed over 80% (173/216) within ±1 dilution range that gives a substantial inter-observer agreement with weighted Fleiss' kappa. By using the EUCAST clinical breakpoints, we defined susceptibility profiles of MICy that were identical to microdilution in more than 92% (197/213) of the decisions. MICy resulted 8.7% major and 3.2% very major discrepancies. MICy is a new, simple FC-based AST method that produces susceptibility profile with low failure rate a workday earlier than the microdilution method. IMPORTANCE MICy is a new, simple and rapid flow cytometry based antibiotic susceptibility testing (AST) method that produces susceptibility profile a workday earlier than the microdilution method or other classical phenotypic AST methods. Shortening the length of AST can accelerate clinical decision-making as targeted antibiotic treatment improves clinical outcomes and reduces mortality, duration of artificial ventilation, and length of stay in intensive care unit. It can also reduce nursing time and costs and the spreading of antibiotic resistance. In this study, we present the workflow and methodology of MICy and compare the results produced by MICy to microdilution step by step.

The efficacy of virtual distance training of intensive therapy and anaesthesiology among fifth-year medical students during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: The coronavirus disease (COVID-19) brought several challenges in medical education. The aim of our study was to investigate whether virtual distance trainings (VDT) organized during the COVID-19 pandemic at our university were effective in replacing in-person bed-side education in intensive therapy and anaesthesiology among fifth-year medical students, both from students' and instructors' perspectives. METHODS: This was a cross-sectional study consisting of three parts: a 20-item students' questionnaire filled out by students participating in VDT, a 22-item instructors' questionnaire filled out by instructors taking part in virtual distance education and a 20-item knowledge test completed by students participating in VDT, as well as by students visiting bed-side trainings (BT) during the same semester, before COVID-19 pandemic. The questionnaires focused on effectiveness, content, self-preparedness, technical background and interactivity of VDT. Instructors' and students' responses given to the common questions, as well as the knowledge test results were compared. Mann-Whitney U test was used for group comparisons and binary logistic regression was performed to analyze the influence of previous health-care experience on students' feeling of self-preparedness. RESULTS: One hundred thirthen students (response rate {RR}: 68%) and 29 instructors (RR: 97%) filled out the questionnaires. The majority of students found our VDT useful and effective; however, a considerable number of participants felt disadvantaged by taking VDT instead of BT sessions and would recommend keeping virtual distance education methods combined with BT. Instructors found VDT overall effective and deemed the transfer of their knowledge satisfactory; however, they described worse interactivity and contact with students during virtual sessions compared to in-person teaching. Instructors showed a clearer consensus that VDT should not replace BT in the future, while students' answers were more divided in this regard. Previous health-care experience did not influence students' feeling of self-preparedness. One hundred and twenty-seven students (56 after VDT {RR: 34%}; 71 after BT {RR: 67%}) completed the end-of-semester knowledge test. Students attending VDT performed better than students visiting BT (median score VDT:83.5 vs BT:77.3; p = 0.015). CONCLUSIONS: Virtual distance learning incorporating virtual practice sessions was effective in maintaining continuous education of intensive therapy and anaesthesiology among fifth-year medical students during the COVID-19 outbreak.

An Interaction Effect Analysis of Thermodilution-Guided Hemodynamic Optimization, Patient Condition, and Mortality after Successful Cardiopulmonary Resuscitation.

Proper hemodynamic management is necessary among post-cardiac arrest patients to improve survival. We aimed to investigate the effects of PiCCO™-guided (pulse index contour cardiac output) hemodynamic management on mortality in post-resuscitation therapy. In this longitudinal analysis of 63 comatose patients after successful cardiopulmonary resuscitation cooled to 32-34 °C, 33 patients received PiCCO™, and 30 were not monitored with PiCCO™. Primary and secondary outcomes were 30 day and 1 year mortality. Kaplan-Meier curves and log-rank tests were used to assess differences in mortality among the groups. Interaction effects to disentangle the relationship between patient's condition, PiCCO™ application, and mortality were assessed by means of Chi-square tests and logistic regression models. A 30 day mortality was significantly higher among PiCCO™ patients, while 1 year mortality was marginally higher. More severe patient condition per se was not the cause of higher mortality rate in the PiCCO™ group. Patients in better health conditions (without ST-elevation myocardial infarction, without cardiogenic shock, without intra-aortic balloon pump device, or without stroke in prior history) had worse outcomes with PiCCO™-guided therapy. Catecholamine administration worsened both 30 day and 1 year mortality among all patients. Our analysis showed that there was a complex interaction relationship between PiCCO™-guided therapy, patients' condition, and 30 day mortality for most conditions.

The timing of testing influences skill retention after basic life support training: a prospective quasi-experimental study.

BACKGROUND: Proper basic life support (BLS) is key in improving the survival of out-of-hospital cardiac arrest. BLS skills deteriorate in three to 6 months after training. One method to improve skill retention may be using the "testing effect" to test skills at the end of a BLS course. The aim of our study was to investigate whether either testing or the timing of such testing after BLS training have any influence on skill retention. METHODS: This was a post-test only, partial coverage, prospective quasi-experimental study designed to evaluate a BLS training course among 464 fifth year medical students at Semmelweis University in the first semester of 2013/2014. Groups were systematically but non-randomly assigned to either a control group that took no exam or one of two experimental groups that took an exam (N = 179, NoExam group; N = 165, EndExam group - exam at the end of the BLS training; N = 120, 3mExam group - exam 3 months after the BLS training). The ability to perform ten prescribed essential BLS steps was evaluated during a skill retention assessment 2 months after the course in the NoExam, 2 months after the course (and the exam) in the EndExam and 5 months after the course (2 months after the exam) in the 3mExam group to measure skill retention and the effect of our intervention. Scores were calculated for each BLS step, and also summed up as a total score. We used Kruskal-Wallis test to assess differences in skill retention. RESULTS: Overall, NoExam and EndExam groups showed similar skill retention. The mean total score (and many of the sub-scores) of students was significantly higher in the 3mExam group compared to both the NoExam and the EndExam groups, and there was no difference in the total score (and many of the sub-scores) of the latter two groups. The 3mExam group had less variability in total scores (and many of the sub-scores) than the other two groups. CONCLUSION: Our study provides evidence that testing these skills 3 months after BLS training may be more effective than either testing immediately at the end of the course or no testing at all.

N-acetylcysteine for sepsis and systemic inflammatory response in adults.

BACKGROUND: Death is common in systemic inflammatory response syndrome (SIRS) or sepsis-induced multisystem organ failure and it has been thought that antioxidants such as N-acetylcysteine could be beneficial. OBJECTIVES: We assessed the clinical effectiveness of intravenous N-acetylcysteine for the treatment of patients with SIRS or sepsis. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue 12); MEDLINE (January 1950 to January 2012); EMBASE (January 1980 to January 2012); CINAHL (1982 to January 2012); the NHS Trusts Clinical Trials Register and Current Controlled Trials (www.controlled-trials.com); LILACS; KoreaMED; MEDCARIB; INDMED; PANTELEIMON; Ingenta; ISI Web of Knowledge and the National Trials Register to identify all relevant randomized controlled trials available for review. SELECTION CRITERIA: We included only randomized controlled trials (RCTs) in the meta-analysis. DATA COLLECTION AND ANALYSIS: We independently performed study selection, quality assessment and data extraction. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. MAIN RESULTS: We included 41 fully published studies (2768 patients). Mortality was similar in the N-acetylcysteine group and the placebo group (RR 1.06, 95% CI 0.79 to 1.42; I(2) = 0%). Neither did N-acetylcysteine show any significant effect on length of stay, duration of mechanical ventilation or incidence of new organ failure. Early application of N-acetylcysteine to prevent the development of an oxidato-inflammatory response did not affect the outcome, nor did late application that is after 24 hours of developing symptoms. Late application was associated with cardiovascular instability. AUTHORS' CONCLUSIONS: Overall, this meta-analysis puts doubt on the safety and utility of intravenous N-acetylcysteine as an adjuvant therapy in SIRS and sepsis. At best, N-acetylcysteine is ineffective in reducing mortality and complications in this patient population. At worst, it can be harmful, especially when administered later than 24 hours after the onset of symptoms, by causing cardiovascular depression. Unless future RCTs provide evidence of treatment effect, clinicians should not routinely use intravenous N-acetylcysteine in SIRS or sepsis and academics should not promote its use.

Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock*.

OBJECTIVE: Controversial data are available on the effects of hydrogen sulfide during hemorrhage. Because the clinical significance of hydrogen sulfide administration in rodents may not be applicable to larger species, we tested the hypothesis whether intravenous Na2S (sulfide) would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation. DESIGN: Prospective, controlled, randomized study. SETTING: University animal research laboratory. SUBJECTS: Forty-five domestic pigs of either gender. INTERVENTIONS: Anesthetized and instrumented animals underwent 4 hrs of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Sulfide infusion was started 2 hrs before hemorrhage, simultaneously with blood removal or at the beginning of retransfusion of shed blood, and continued for 12 hrs. Resuscitation comprised hydroxyethyl starch and norepinenephrine infusion titrated to maintain mean arterial pressure at preshock values. MEASUREMENTS AND MAIN RESULTS: Before, immediately at the end of and 12 and 22 hrs after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, nitric oxide and cytokine production (nitrate+nitrite, interleukin-6, tumor necrosis factor-α levels). Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and DNA damage (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining). The progressive kidney (creatinine levels, creatinine clearance), liver (transaminase activities, bilirubin levels), and cardiocirculatory (norepipnehrine requirements, troponin I levels) dysfunction was attenuated in the simultaneous treatment group only, which coincided with reduced lung, liver, and kidney histological damage. Sulfide reduced mortality, however, irrespective of the timing of its administration. CONCLUSIONS: While the sulfide-induced protection against organ injury was only present when initiated simultaneously with blood removal, it was largely unrelated to hypothermia. The absence of sulfide-mediated protection in the pretreatment protocol may be due to the accumulation of sulfide during low flow states. In conclusion, sulfide treatment can be effective in hemorrhagic shock, but its effectiveness is restricted to a narrow timing and dosing window.

Transpulmonary thermodilution in neonates undergoing arterial switch surgery.

Measurement of the global end-diastolic volume index (GEDI) by transpulmonary thermodilution (TPTD) has become a useful technique for measuring preload in adults. This study aimed to investigate the hemodynamic changes in neonates during the postoperative period after arterial switch surgery. Over a 13-month period, the postoperative data of 12 neonates with transposition of the great arteries were retrospectively investigated. Arterial and central venous blood pressures were monitored, Cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index (SVRI), GEDI, and extravascular lung water index (ELWI) were measured by thermodilution. The CI was significantly correlated with the SVRI only in the closed chest condition (r = -0.92; P < 0.001). The CI and SVI values were significantly lower and the ELWI and SVRI values significantly higher in both the open and closed chest conditions than the postextubation values. The relationship between change in GEDI and change in CI was stronger in the open chest condition (r = 0.93; P < 0.006) than in the closed chest condition (r = 0.75; P = 0.055). However, the latter just missed statistical significance. According to the findings, TPTD seems to be a useful tool for assessing cardiac function after neonatal arterial switch surgery. Establishment of normal values will be essential for proper guidance of therapy for this population using volumetric parameters.

Effects of intravenous sulfide during porcine aortic occlusion-induced kidney ischemia/reperfusion injury.

In rodents, inhaled H2S and injection of H2S donors protected against kidney ischemia/reperfusion (I/R) injury. During porcine aortic occlusion, the H2S donor Na2S (sulfide) reduced energy expenditure and decreased the noradrenaline requirements needed to maintain hemodynamic targets during early reperfusion. Therefore, we tested the hypothesis whether sulfide pretreatment may also ameliorate organ function in porcine aortic occlusion-induced kidney I/R injury. Anesthetized, ventilated, and instrumented pigs randomly received either sulfide or vehicle and underwent 90 min of kidney ischemia using intraaortic balloon-occlusion, and 8 h of reperfusion. During reperfusion, noradrenaline was titrated to maintain blood pressure at baseline levels. Sulfide attenuated the fall in creatinine clearance and the rise in creatinine blood levels, whereas renal blood flow and fractional Na+ excretion were comparable. Sulfide also lowered the blood IL-6, IL-1ß, and nitrite + nitrate concentrations, which coincided with reduced kidney oxidative DNA base damage and iNOS expression, and attenuated glomerular histological injury as assessed by the incidence of glomerular tubularization. While expression of heme oxygenase 1 and cleaved caspase 3 did not differ, sulfide reduced the expression Bcl-xL and increased the activation of nuclear transcription factor κB. During porcine aortic occlusion-induced kidney I/R injury, sulfide pretreatment attenuated tissue injury and organ dysfunction as a result of reduced inflammation and oxidative and nitrosative stress. The higher nuclear transcription factor κB activation was probably due to the drop in temperature.

Right man, right time, right place?--on the time course of the mediator orchestra in septic shock.

Appropriate timing of treatment assumes particular importance in critical care. Lange and colleagues recently reported on the time course of the different nitric oxide synthase (NOS) isoforms, nitrosative stress, and poly(ADP-ribosylation) during Pseudomonas aeruginosa pneumonia-induced ovine septic shock. Initially, endothelial NOS expression was increased together with markers of peroxynitrite formation, DNA damage, and nuclear factor-kappa-B activation. Later on, measurable NOS activity and nitric oxide production resulted mainly from inducible NOS activation. These results emphasize the need for long-term, large-animal studies investigated over days so that future therapeutic interventions can be better tailored and matched to the exact time course of the activation of the mediator orchestra.

Infrared ear thermometry in water-related accidents-not a good choice.

Hypothermia in near-drowning victims is a serious problem that impacts clinical decision-making. The purpose of this trial was to determine the reliability of tympanic temperature measurements compared to oral temperature measurements after immersion in water. After ethical approval was obtained, we studied oral and tympanic temperature in 25 volunteer swimmers (aged 18-49 years). Sublingual (Fixotherm; Tradesell Europe, Eglharting, Germany) and tympanic (First Temp Genius; Sherwood Medical, Sulzbach, Germany) temperature measurements were performed before entering the water, after 45 min of immersion in water, and 15 min after leaving the water. During the immersion phase, the ears were temporarily immersed. A control group (the same 25 volunteers) had to swim for the same amount of time without ever immersing their heads in the water. The trial was performed in an indoor swimming pool at 28 degrees C water and 30 degrees C air temperature. The oral temperature did not change over time in either group. The tympanic temperature was significantly lower after immersion compared to baseline in the "immersed" group (33.7 degrees C vs. 37.5 degrees C, p < 0.001), increased significantly in the recovery period, but remained significantly lower than baseline (36.0 degrees C vs. 37.5 degrees C, p < 0.001). At baseline, the oral temperature was lower compared to the tympanic temperature. This relationship reversed after immersion and remained reversed until the end of the trial in the immersion group. The control group maintained oral temperatures lower than tympanic throughout the study; furthermore, the control group had no clinically relevant change in oral or tympanic temperature over the time (tympanic temperature: 37.4 degrees C vs. 37.2 degrees C, p = 0.06). Our data suggest that in water-related accidents such as near drowning, the values of body (core) temperature obtained via use of infrared ear thermometry are unreliable, and should not be used for clinical decision-making.

Comparison of cardiac, hepatic, and renal effects of arginine vasopressin and noradrenaline during porcine fecal peritonitis: a randomized controlled trial.

INTRODUCTION: Infusing arginine vasopressin (AVP) in vasodilatory shock usually decreases cardiac output and thus systemic oxygen transport. It is still a matter of debate whether this vasoconstriction impedes visceral organ blood flow and thereby causes organ dysfunction and injury. Therefore, we tested the hypothesis whether low-dose AVP is safe with respect to liver, kidney, and heart function and organ injury during resuscitated septic shock. METHODS: After intraperitoneal inoculation of autologous feces, 24 anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned to noradrenaline alone (increments of 0.05 microg/kg/min until maximal heart rate of 160 beats/min; n = 12) or AVP (1 to 5 ng/kg/min; supplemented by noradrenaline if the maximal AVP dosage failed to maintain mean blood pressure; n = 12) to treat sepsis-associated hypotension. Parameters of systemic and regional hemodynamics (ultrasound flow probes on the portal vein and hepatic artery), oxygen transport, metabolism (endogenous glucose production and whole body glucose oxidation derived from blood glucose isotope and expiratory 13CO2/12CO2 enrichment during 1,2,3,4,5,6-13C6-glucose infusion), visceral organ function (blood transaminase activities, bilirubin and creatinine concentrations, creatinine clearance, fractional Na+ excretion), nitric oxide (exhaled NO and blood nitrate + nitrite levels) and cytokine production (interleukin-6 and tumor necrosis factor-alpha blood levels), and myocardial function (left ventricular dp/dtmax and dp/dtmin) and injury (troponin I blood levels) were measured before and 12, 18, and 24 hours after peritonitis induction. Immediate post mortem liver and kidney biopsies were analysed for histomorphology (hematoxylin eosin staining) and apoptosis (TUNEL staining). RESULTS: AVP decreased heart rate and cardiac output without otherwise affecting heart function and significantly decreased troponin I blood levels. AVP increased the rate of direct, aerobic glucose oxidation and reduced hyperlactatemia, which coincided with less severe kidney dysfunction and liver injury, attenuated systemic inflammation, and decreased kidney tubular apoptosis. CONCLUSIONS: During well-resuscitated septic shock low-dose AVP appears to be safe with respect to myocardial function and heart injury and reduces kidney and liver damage. It remains to be elucidated whether this is due to the treatment per se and/or to the decreased exogenous catecholamine requirements.

Hemodynamic, metabolic, and organ function effects of pure oxygen ventilation during established fecal peritonitis-induced septic shock.

OBJECTIVE: To test the hypothesis whether pure oxygen ventilation is equally safe and beneficial in fully developed fecal peritonitis-induced septic shock as hyperoxia initiated at the induction of sepsis. DESIGN: Prospective, randomized, controlled, experimental study with repeated measures. SETTING: Animal research laboratory at a university medical school. SUBJECTS: Twenty anesthetized, mechanically ventilated, and instrumented pigs. INTERVENTIONS: Twelve hours after induction of fecal peritonitis by inoculation of autologous feces, swine, which were resuscitated with hydroxyethyl starch and norepinephrine to maintain mean arterial pressure at baseline values, were ventilated randomly with an Fio2 required to keep Sao2 >90% (controls: n = 10) or Fio2 1.0 (hyperoxia, n = 10) during the next 12 hrs. MEASUREMENTS AND MAIN RESULTS: Despite similar hemodynamic support (hydroxyethyl starch and norepinephrine doses), systemic and regional macrocirculatory and oxygen transport parameters, hyperoxia attenuated pulmonary hypertension, improved gut microcirculation (ileal mucosal laser Doppler flowmetry) and portal venous acidosis, prevented the deterioration in creatinine clearance (controls 61 (44;112), hyperoxia: 96 (88;110) mL.min(-1), p = .074), and attenuated the increase in blood tumor necrosis factor-alpha concentrations (p = .045 and p = .112 vs. controls at 18 hrs and 24 hrs, respectively). Lung and liver histology (hematoxyline eosine staining) were comparable in the two groups, but hyperoxia reduced apoptosis (Tunel test) in the liver (4 (3;8) vs. 2 (1;5) apoptotic cells/field, p = .069) and the lung (36 (31;46) vs. 15 (13;17) apoptotic cells/field, p < .001). Parameters of lung function, tissue antioxidant activity, blood oxidative and nitrosative stress (nitrate + nitrite, 8-isoprostane levels; deoxyribonucleic acid (DNA) damage measured using the comet assay) were not further affected during hyperoxia. CONCLUSIONS: When compared with the previous report on hyperoxia initiated simultaneously with induction of sepsis, i.e., using a pretreatment approach, pure oxygen ventilation started when porcine fecal peritonitis-induced septic shock was fully developed proved to be equally safe with respect to lung function and oxidative stress, but exerted only moderate beneficial effects.

Vasopressin in vasodilatory shock: is the heart in danger?

In patients with hyperdynamic hemodynamics, infusing arginine vasopressin (AVP) in advanced vasodilatory shock is usually accompanied by a decrease in cardiac output and in visceral organ blood flow. Depending on the infusion rate, this vasoconstriction also reduces coronary blood flow despite an increased coronary perfusion pressure. In a porcine model of transitory myocardial ischemia-induced left ventricular dysfunction, Müller and colleagues now report that the AVP-related coronary vaso-constriction may impede diastolic relaxation while systolic contraction remains unaffected. Although any AVP-induced myocardial ischemia undoubtedly is a crucial safety issue, these findings need to be discussed in the context of the model design, the dosing of AVP as well as the complex direct, afterload-independent and systemic, vasoconstriction-related effects on the heart.

Nitric oxide, leukocytes and microvascular permeability: causality or bystanders?

Increased microvascular permeability resulting in tissue edema is a hallmark of sepsis-related microcirculatory failure, and leukocyte-endothelium interaction is thought to assume major importance in this context. However, the role of nitric oxide (NO) in the interplay of inflammation, leukocyte-endothelium interaction and increased microcirculatory permeability is still a matter of debate. Hollenberg et al. now report, in the previous issue of Critical Care, that neither genetic deletion nor pharmacologic blockade of the inducible isoform of the NO synthase (iNOS) affected the sepsis-related aggravation of leukocyte rolling and adhesion, whereas iNOS inhibition attenuated microvascular permeability. The authors conclude that excess NO resulting from iNOS activation is important in modulating vascular permeability during sepsis, but that this effect is independent of its action on leukocytes.

Effects of intrarenal administration of the calcium antagonist nimodipine during porcine aortic occlusion-induced ischemia/reperfusion injury.

Ca++ antagonists have been tested to improve I/R injury in the kidney, but their clinical use is limited due to their hypotensive properties. Therefore, we tested the hypothesis on whether infusing the Ca++ blocker nimodipine directly into the renal artery would reduce kidney cell apoptosis and thus improve organ function in a porcine model of suprarenal abdominal aortic cross-clamping. In a prospective, randomized, controlled, blinded study, anesthetized, mechanically ventilated, and instrumented pigs underwent 45 min of suprarenal aortic cross-clamping animals receiving either 0.25 microg kg(-1) min(-1) nimodipine (n = 8) or vehicle (n = 8). Systemic and right kidney hemodynamics, oxygen exchange, and metabolism were assessed before clamping, as well as before and at 75 and 195 min of reperfusion (i.e., at 120 and 240 min after aortic occlusion). At the end of the experiments, the right kidney was harvested for conventional hematoxylineosin staining and immunohistochemistry for the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) gene expression and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin end labeling test). Neither systemic nor renal hemodynamics and oxygen exchange, plasma and urine protein concentrations, urine osmolarity, and lactate-pyruvate ratios showed any intergroup difference. Nimodipine infusion resulted in a significantly higher creatinine clearance after 195 min of reperfusion (26 [17 - 42] vs. 17 [9 - 22] mL x min(-1)) and attenuated renal tubular damage, as indicated by lower urinary small protein (25 kd) concentrations. Improved renal function was concomitant with significantly less pronounced positive nuclear terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin end labeling staining. In a porcine model of suprarenal aortic cross-clamping, intrarenal nimodipine infusion improved postischemia kidney function, most likely as a result of attenuated glomerular apoptosis.

The selective poly(ADP)ribose-polymerase 1 inhibitor INO1001 reduces spinal cord injury during porcine aortic cross-clamping-induced ischemia/reperfusion injury.

OBJECTIVE: It is well-established that poly(ADP)ribose-polymerase (PARP) assumes major importance during ischemic brain damage, and the selective PARP-1 inhibitor PJ34 reduced spinal cord damage in murine aortic occlusion-induced ischemia/reperfusion injury. We investigated the effect of the PARP-1 inhibitor INO1001 on aortic-occlusion-related porcine spinal cord injury. DESIGN AND SETTING: Prospective, randomized, controlled experimental study in an animal laboratory. PATIENTS AND PARTICIPANTS: Ten anesthetized, mechanically ventilated, and instrumented pigs. INTERVENTIONS: Animals underwent 45 min of thoracic aortic cross-clamping after receiving vehicle (n=5) or intravenous INO1001 (n=5, total dose 4 mg/kg administered both before clamping and during reperfusion). During reperfusion continuous intravenous norepinephrine was incrementally adjusted to maintain blood pressure at or above 80% of the preclamping level. Plasma INO1001 levels were analyzed by HPLC. After 4[Symbol: see text]h of reperfusion spinal cord biopsy samples were analyzed for neuronal damage (hematoxyline-eosine and Nissl staining), expression of the cyclin-dependent kinase inhibitor genes p21 and p27 (immunohistochemistry), and apoptosis (terminal deoxynucleotidyl transferase mediated nick end labeling assay). MEASUREMENTS AND RESULTS: Plasma INO1001 levels were 0.8-2.3 and 0.30-0.76 mM before and after clamping, respectively. While 3-5% of the spinal cord neurons were irreversibly damaged in the INO1001 animals, the neuronal cell injury was three times higher in the control group. Neither p21 and p27 expression nor apoptosis showed any intergroup difference. CONCLUSIONS: The selective PARP-1 inhibitor INO1001 markedly reduced aortic occlusion-induced spinal cord injury. Given the close correlation reported in the literature between morphological damage and impaired spinal cord function, INO1001 may improve spinal cord recovery after thoracic aortic cross-clamping.