Search

A 54-year-old male patient was admitted to the hospital due to symptoms caused by an intramural hematoma of the descending aorta. In a contrast media-enhanced computed tomography scan performed five days after admission to evaluate dynamics of the hematoma, a hyperdense lesion was seen in the stomach. A suspicion of gastric hemorrhage was raised at the first evaluation. Because the patient’s clinical condition and hemoglobin levels were stable, gastroscopy to rule out an aorto-gastric fistula or another type of bleeding was not undertaken. In the secondary evaluation of the history and images, it became clear that the hyperdense lesion mimicking bleeding in the stomach must have been caused by a degrading potassium tablet ingested by the patient five hours before the investigation.

Context Glucocorticoids regulate hemostatic and endothelial function, and they are critical for adaptive functions during surgery. No data regarding the impact of adrenal function on hemostasis and endothelial function in the perioperative setting are available. Objective We assessed the association of adrenal response to adrenocorticotropic hormone (ACTH) and markers of endothelial/hemostatic function in surgical patients. Methods This prospective observational study, conducted at a tertiary care hospital, included 60 patients (35 male/25 female) undergoing abdominal surgery. Adrenal function was evaluated by low-dose ACTH stimulation test on the day before, during, and the day after surgery. According to their stimulated cortisol level (cutoff ≥ 500 nmol/L), patients were classified as having normal hypothalamic-pituitary-adrenal (HPA)-axis function (nHPA) or deficient HPA-axis function (dHPA). Parameters of endothelial function (soluble vascular cell adhesion molecule-1, thrombomodulin) and hemostasis (fibrinogen, von Willebrand factor antigen, factor VIII [FVIII]) were measured during surgery. Results Twenty-one patients had dHPA and 39 had nHPA. Compared with nHPA, patients with dHPA had significantly lower peak cortisol before (median 568 vs 425 nmol/L, P Conclusions Patients with dHPA undergoing abdominal surgery demonstrate impaired hemostasis which can translate into excessive blood loss.

Mambas (genusDendroaspis) are among the most feared venomous African snakes. Without medical treatment, mamba bites are frequently fatal. First-aid treatment includes lymphatic retardation with the pressure immobilization technique. Medical management comprises continuous monitoring, securing patency of the airway, ensuring adequate ventilation, symptomatic measures, and administration of specific antivenin. We report an unusual case of a snake breeder bitten by a black mamba in Switzerland, report the clinical course, and review the lifesaving emergency management of mamba bites. This case highlights the importance of early antivenin administration and suggests that emergency and critical care physicians as well as first responders all around the world should be familiar with clinical toxinology of exotic snake bites as well as with the logistics to most rapidly make the specific antivenin available.

Introduction: Repeated diaphragm compound muscle action potential (CMAP) recordings may help to understand the pathophysiology of respiratory muscle weakness. Neurally adjusted ventilator assist (NAVA) uses esophageal EMG electrodes to drive the ventilator. We evaluated the feasibility of CMAP recordings using these electrodes and established normal values. Methods: Bilateral cervical phrenic nerve electrical stimulation was performed in 15 healthy volunteers. CMAP recordings with esophageal NAVA electrodes were compared with surface electrode recordings during inspiratory and expiratory pause. Results: Compared with surface recordings, esophageal CMAP amplitudes were higher with increased latencies. Differences between the 2 techniques were most prominent in inspiration. For both recording techniques, amplitudes were higher, and latencies were longer during inspiration. Latencies were also longer when measured on the left side. Conclusions: Diaphragm CMAPs can be measured using the commercially available esophageal NAVA probe. This may facilitate repeated diaphragm CMAP studies in mechanically ventilated patients. Muscle Nerve 51: 598–600, 2015

BACKGROUND Endogenous pulmonary reflexes may protect the lungs during mechanical ventilation. We aimed to assess integration of continuous neurally adjusted ventilatory assist (cNAVA), delivering assist in proportion to diaphragm's electrical activity during inspiration and expiration, and Hering-Breuer inflation and deflation reflexes on lung recruitment, distension, and aeration before and after acute lung injury (ALI). METHODS In 7 anesthetised rabbits with bilateral pneumothoraces, we identified adequate cNAVA level (cNAVAAL) at the plateau in peak ventilator pressure during titration procedures before (healthy lungs with endotracheal tube, [HLETT]) and after ALI (endotracheal tube [ALIETT] and during non-invasive ventilation [ALINIV]). Following titration, cNAVAAL was maintained for 5minutes. In 2 rabbits, procedures were repeated after vagotomy (ALIETT+VAG). In 3 rabbits delivery of assist was temporarily modulated to provide assist on inspiration only. Computed tomography was performed before intubation, before ALI, during cNAVA titration, and after maintenance at cNAVAAL. RESULTS During ALIETT and ALINIV, normally aerated lung-regions doubled and poorly aerated lung-regions decreased to less than a third (p

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27 h of faecal peritonitis and to a control condition (n = 9 each group). At the end, hepatic mitochondria were isolated and incubated for one hour with either norepinephrine or placebo, with and without pretreatment with the specific receptor antagonists prazosin and yohimbine. Mitochondrial state 3 and state 4 respiration were measured for respiratory chain complexes I and II, and state 3 for complex IV using high-resolution respirometry, and respiratory control ratios were calculated. Additionally, skeletal muscle mitochondrial respiration was evaluated after incubation with norepinephrine and dobutamine with and without the respective antagonists (atenolol, propranolol and phentolamine for dobutamine). Faecal peritonitis was characterized by decreasing blood pressure and stroke volume, and maintained systemic oxygen consumption. Neither faecal peritonitis nor any of the drugs or drug combinations had measurable effects on hepatic or skeletal muscle mitochondrial respiration. Norepinephrine did not improve the efficiency of complex I- and complex II-dependent isolated hepatic mitochondrial respiration [respiratory control ratio (RCR) complex I: 5.6 ± 5.3 (placebo) vs. 5.4 ± 4.6 (norepinephrine) in controls and 2.7 ± 2.1 (placebo) vs. 2.9 ± 1.5 (norepinephrine) in septic animals; RCR complex II: 3.5 ± 2.0 (placebo) vs. 3.5 ± 1.8 (norepinephrine) in controls; 2.3 ± 1.6 (placebo) vs. 2.2 ± 1.1 (norepinephrine) in septic animals]. Prolonged faecal peritonitis did not affect either hepatic or skeletal muscle mitochondrial respiration. Subsequent incubation of isolated mitochondria with norepinephrine and dobutamine did not significantly influence their respiration.

Repeated diaphragm compound muscle action potential (CMAP) recordings may help to understand the pathophysiology of respiratory muscle weakness. Neurally adjusted ventilator assist (NAVA) uses esophageal EMG electrodes to drive the ventilator. We evaluated the feasibility of CMAP recordings using these electrodes and established normal values.Bilateral cervical phrenic nerve electrical stimulation was performed in 15 healthy volunteers. CMAP recordings with esophageal NAVA electrodes were compared with surface electrode recordings during inspiratory and expiratory pause.Compared with surface recordings, esophageal CMAP amplitudes were higher with increased latencies. Differences between the 2 techniques were most prominent in inspiration. For both recording techniques, amplitudes were higher, and latencies were longer during inspiration. Latencies were also longer when measured on the left side.Diaphragm CMAPs can be measured using the commercially available esophageal NAVA probe. This may facilitate repeated diaphragm CMAP studies in mechanically ventilated patients.

Objective To evaluate the influence of neurally adjusted ventilatory assist (NAVA) and positive end-expiratory pressure (PEEP) on the control of breathing in rabbits with acute lung injury. Design Prospective animal study. Setting Experimental laboratory in a university hospital. Subjects Male White New Zealand rabbits (n = 18). Intervention Spontaneously breathing rabbits with hydrochloric acid-induced lung injury were ventilated with NAVA and underwent changes in NAVA gain and PEEP (six nonvagotomized and five vagotomized). Seven other nonvagotomized rabbits underwent 4 hrs of ventilation with hourly titration of PEEP, Fio2, and NAVA gain. Measurements and main results We studied diaphragm electrical activity, respiratory pressures, and breathing pattern. After lung injury, 0 cm H2O of PEEP resulted in high tonic and no discernible phasic diaphragm electrical activity in the nonvagotomized rabbits; stepwise increases in PEEP (up to 11.7 +/- 2.6 cm H2O) reduced tonic but increased phasic diaphragm electrical activity. Increasing the NAVA gain reduced phasic diaphragm electrical activity to almost half and abolished esophageal pressure swings. Tidal volume remained at 4-5 mL/kg, and respiratory rate did not change. In the vagotomized group, lung injury did not induce tonic activity, and phasic activity and tidal volume were several times higher than in the nonvagotomized rabbits. Four hours of breathing with NAVA restored breathing pattern and neural and mechanical breathing efforts to pre-lung injury levels. Conclusions Acute lung injury can cause a vagally mediated atypical diaphragm activation pattern in spontaneously breathing rabbits. Modulation of PEEP facilitates development of phasic diaphragm electrical activity, whereupon implementation of NAVA can efficiently maintain unloading of the respiratory muscles without delivering excessive tidal volume in rabbits with intact vagal function.

OBJECTIVE: Measuring peritoneal lactate concentrations could be useful for detecting splanchnic hypoperfusion. The aims of this study were to evaluate the properties of a new membrane-based microdialyzer in vitro and to assess the ability of the dialyzer to detect a clinically relevant decrease in splanchnic blood flow in vivo. DESIGN: A membrane-based microdialyzer was first validated in vitro. The same device was tested afterward in a randomized, controlled animal experiment. SETTING: University experimental research laboratory. SUBJECTS: Twenty-four Landrace pigs of both genders. INTERVENTIONS: In vitro: Membrane microdialyzers were kept in warmed sodium lactate baths with lactate concentrations between 2 and 8 mmol/L for 10-120 mins, and microdialysis lactate concentrations were measured repeatedly (210 measurements). In vivo: An extracorporeal shunt with blood reservoir and roller pump was inserted between the proximal and distal abdominal aorta, and a microdialyzer was inserted intraperitoneally. In 12 animals, total splanchnic blood flow (measured by transit time ultrasound) was reduced by a median 43% (range, 13% to 72%) by activating the shunt; 12 animals served as controls. MEASUREMENTS AND MAIN RESULTS: In vitro: The fractional lactate recovery was 0.59 (0.32-0.83) after 60 mins and 0.82 (0.71-0.87) after 90 mins, with no further increase thereafter. At 60 and 90 mins, the fractional recovery was independent of the lactate concentration. In vivo: Abdominal blood flow reduction resulted in an increase in peritoneal microdialysis lactate concentration from 1.7 (0.3-3.8) mmol/L to 2.8 (1.3-6.2) mmol/L (p = .006). At the same time, mesenteric venous-arterial lactate gradient increased from 0.1 (-0.2-0.8) mmol/L to 0.3 (-0.3 -1.8) mmol/L (p = .032), and mesenteric venous-arterial Pco2 gradients increased from 12 (8-19) torr to 21 (11-54) torr (p = .005). CONCLUSIONS: Peritoneal membrane microdialysis provides a method for the assessment of splanchnic ischemia, with potential for clinical application.

Low cardiac output impairs the hepatic arterial buffer response (HABR). Whether this is due to low abdominal blood flow per se is not known. Dobutamine is commonly used to increase cardiac output, and it may further modify hepatosplanchnic and renal vasoregulation. We assessed the effects of isolated abdominal aortic blood flow changes and dobutamine on hepatosplanchnic and renal blood flow. Twenty-five anesthetized pigs with an abdominal aorto-aortic shunt were randomized to 2 control groups [zero (n = 6) and minimal (n = 6) shunt flow], and 2 groups with 50% reduction of abdominal blood flow and either subsequent increased abdominal blood flow by shunt reduction (n = 6) or dobutamine infusion at 5 and 10 microg kg(-1) min(-1) with constant shunt flow (n = 7). Regional (ultrasound) and local (laser Doppler) intra-abdominal blood flows were measured. The HABR was assessed during acute portal vein occlusion. Sustained low abdominal blood flow, by means of shunt activation, decreased liver, gut, and kidney blood flow similarly and reduced local microcirculatory blood flow in the jejunum. Shunt flow reduction partially restored regional blood flows but not jejunal microcirculatory blood flow. Low-but not high-dose dobutamine increased gut and celiac trunk flow whereas hepatic artery and renal blood flows remained unchanged. Neither intervention altered local blood flows. The HABR was not abolished during sustained low abdominal blood flow despite substantially reduced hepatic arterial blood flow and was not modified by dobutamine. Low-but not high-dose dobutamine redistributes blood flow toward the gut and celiac trunk. The jejunal microcirculatory flow, once impaired, is difficult to restore.

Background: Both hyperlactatemia and persistence of hyperlactatemia have been associated with bad outcome. We compared lactate and lactate-derived variables in outcome prediction.Methods: Retrospective observational study. Case records from 2,251 consecutive intensive care unit (ICU) patients admitted between 2001 and 2007 were analyzed. Baseline characteristics, all lactate measurements, and in-hospital mortality were recorded. The time integral of arterial blood lactate levels above the upper normal threshold of 2.2 mmol/L (lactate-time-integral), maximum lactate (max-lactate), and time-to-first-normalization were calculated. Survivors and nonsurvivors were compared and receiver operating characteristic (ROC) analysis were applied.Results: A total of 20,755 lactate measurements were analyzed. Data are srpehown as median [interquartile range]. In nonsurvivors (n = 405) lactate-time-integral (192 [0-1881] min.mmol/L) and time-to-first normalization (44.0 [0-427] min) were higher than in hospital survivors (n = 1846; 0 [0-134] min.mmol/L and 0 [0-75] min, respectively; all p 6 hours (mortality 16.6% vs. 24.4%; p 0.05). The area under the ROC curves for admission lactate and lactate-time-integral was not different (p = 0.36).Conclusions: Hyperlactatemia is associated with in-hospital mortality in a heterogeneous ICU population. In our patients, lactate peak values predicted in-hospital mortality equally well as lactate-time-integral of arterial blood lactate levels above the upper normal threshold.

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle ( n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle ( n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18–1.32) mmHg/ml vs. 0.22 (0.08–0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia ( P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22–134%) in controls vs. 53% (37–85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12–47%) of baseline ( P = 0.043) vs. 17% (−7–32%) in endotoxemia ( P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

Diaphragmatic electrical activity (EA(di)), reflecting respiratory drive, and its feedback control might be impaired in critical illness-associated polyneuromyopathy (CIPM). We aimed to evaluate whether titration and prolonged application of neurally adjusted ventilatory assist (NAVA), which delivers pressure (P (aw)) in proportion to EA(di), is feasible in CIPM patients.Peripheral and phrenic nerve electrophysiology studies were performed in 15 patients with clinically suspected CIPM and in 14 healthy volunteers. In patients, an adequate NAVA level (NAVAal) was titrated daily and was implemented for a maximum of 72 h. Changes in tidal volume (V (t)) generation per unit of EA(di) (V (t)/EA(di)) were assessed daily during standardized tests of neuro-ventilatory efficiency (NVET).In patients (median [range], 66 [44-80] years), peripheral electrophysiology studies confirmed CIPM. Phrenic nerve latency (PNL) was prolonged and diaphragm compound muscle action potential (CMAP) was reduced compared with healthy volunteers (p 0.05 for both). NAVAal could be titrated in all but two patients. During implementation of NAVAal for 61 (37-64) h, the EA(di) amplitude was 9.0 (4.4-15.2) μV, and the V (t) was 6.5 (3.7-14.3) ml/kg predicted body weight. V (t), respiratory rate, EA(di), PaCO(2), and hemodynamic parameters remained unchanged, while PaO(2)/FiO(2) increased from 238 (121-337) to 282 (150-440) mmHg (p = 0.007) during NAVAal. V (t)/EA(di) changed by -10 (-46; +31)% during the first NVET and by -0.1 (-26; +77)% during the last NVET (p = 0.048).In most patients with CIPM, EA(di) and its feedback control are sufficiently preserved to titrate and implement NAVA for up to 3 days. Whether monitoring neuro-ventilatory efficiency helps inform the weaning process warrants further evaluation.

Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to the electrical activity of the diaphragm (EAdi) using an adjustable proportionality constant (NAVA level, cm⋅H 2O/\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\mu$\end{document}V). During systematic increases in the NAVA level, feedback-controlled down-regulation of the EAdi results in a characteristic two-phased response in Paw and tidal volume (Vt). The transition from the 1st to the 2nd response phase allows identification of adequate unloading of the respiratory muscles with NAVA (NAVAAL). We aimed to develop and validate a mathematical algorithm to identify NAVAAL. Paw, Vt, and EAdi were recorded while systematically increasing the NAVA level in 19 adult patients. In a multistep approach, inspiratory Paw peaks were first identified by dividing the EAdi into inspiratory portions using Gaussian mixture modeling. Two polynomials were then fitted onto the curves of both Paw peaks and Vt. The beginning of the Paw and Vt plateaus, and thus NAVA AL, was identified at the minimum of squared polynomial derivative and polynomial fitting errors. A graphical user interface was developed in the Matlab computing environment. Median NAVAAL visually estimated by 18 independent physicians was 2.7 (range 0.4 to 5.8) cm⋅H 2O/\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\mu$\end{document}V and identified by our model was 2.6 (range 0.6 to 5.0) cm⋅H 2O/\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\mu$\end{document}V. NAVAAL identified by our model was below the range of visually estimated NAVAAL in two instances and was above in one instance. We conclude that our model identifies NAVAAL in most instances with acceptable accuracy for application in clinical routine and research.

To test the hypothesis that muscle fibers are depolarized in patients with critical illness myopathy by measuring velocity recovery cycles (VRCs) of muscle action potentials.VRCs were recorded from brachioradialis muscle by direct muscle stimulation in 10 patients in intensive care with evidence of critical illness myopathy (CIM). Two sets of recordings were made, mean 3.9 d apart, and compared with those from 10 age-matched controls.Muscle supernormality was reduced in the patients by 50% compared with controls (P0.002) and relative refractory period was increased by 59% (P0.01). Supernormality was correlated with plasma potassium levels (R=-0.753, P0.001), and the slope of this relationship was much steeper than previously reported for non-critically ill patients with renal failure (P0.01).The abnormal excitability properties indicate that the muscle fibers in CIM were depolarized, and/or that sodium channel inactivation was increased. The heightened sensitivity to potassium is consistent with the hypothesis that an endotoxin reduces sodium channel availability in depolarized muscle fibers.VRCs provide a practicable means to monitor muscle membrane changes in intensive care and to investigate the pathogenesis of CIM.

Background Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to neural inspiratory drive as reflected by electrical activity of the diaphragm (EAdi). Changing positive end-expiratory pressure (PEEP) impacts respiratory muscle load and function and, hence, EAdi. We aimed to evaluate how PEEP affects the breathing pattern and neuroventilatory efficiency during NAVA. Methods In 20 adult patients, adequate assist (NAVAal) was first identified based on Paw and tidal volume (V t ) responses to systematic increases in NAVA level while using preset PEEP (PEEPbl). Thereafter, using NAVAal, PEEP was increased to 20 cm water (H 2 O) (PEEPhigh) and then lowered stepwise to 1 cm H 2 O (PEEP1). EAdi, Paw, and V t were recorded. Results Median NAVAal was 2.7 (interquartile range, 2.3–3.5) cm H 2 O/μV and was similar to NAVAal identified post hoc by 17 independent physicians (2.5 [2.0–3.4] cm H 2 O/μV; P = NS). Reducing PEEPhigh to PEEP1 increased inspiratory EAdi by 34% (2–67; P = .046) and was associated with an increase in mean Paw above PEEP from 8.5 (6.7–11.4) cm H 2 O to 12.2 (8.8–16.7) cm H 2 O ( P = .008), whereas V t and respiratory rate remained unchanged. The response pattern in V t /EAdi, indicating changes in neuroventilatory efficiency, differed among patients. Tidal breathing occurred at the lowest EAdi cost in seven patients with PEEP1 or half PEEPbl, in six patients with PEEPbl, and in seven patients with PEEPhigh. Conclusions During NAVAal, increasing PEEP reduces respiratory drive. Patients adapt their neuroventilatory efficiency such that the individual ventilatory pattern is preserved over a wide range of PEEP levels. Monitoring V t /EAdi during PEEP changes allows identification of a PEEP level at which tidal breathing occurs at minimal EAdi cost. Trial registration clinicaltrials.gov ; Identifier: NCT00529347

OBJECTIVE: To determine if neurally adjusted ventilatory assist (NAVA) that delivers pressure in proportion to diaphragm electrical activity is as protective to acutely injured lungs (ALI) and non-pulmonary organs as volume controlled (VC), low tidal volume (Vt), high positive end-expiratory pressure (PEEP) ventilation. DESIGN: Prospective, randomized, laboratory animal study. SUBJECTS: Twenty-seven male New Zealand white rabbits. INTERVENTIONS: Anesthetized rabbits with hydrochloric acid-induced ALI were randomized (n = 9 per group) to 5.5 h NAVA (non-paralyzed), VC (paralyzed; Vt 6-ml/kg), or VC (paralyzed; Vt 15-ml/kg). PEEP was adjusted to hemodynamic goals in NAVA and VC6-ml/kg, and was 1 cmH2O in VC15-ml/kg. MEASUREMENTS AND MAIN RESULTS: PaO2/FiO2; lung wet-to-dry ratio; lung histology; interleukin-8 (IL-8) concentrations in broncho-alveolar-lavage (BAL) fluid, plasma, and non-pulmonary organs; plasminogen activator inhibitor type-1 and tissue factor in BAL fluid and plasma; non-pulmonary organ apoptosis rate; creatinine clearance; echocardiography. PEEP was similar in NAVA and VC6-ml/kg. During NAVA, Vt was lower (3.1 +/- 0.9 ml/kg), whereas PaO2/ FiO2, respiratory rate, and PaCO2 were higher compared to VC6-ml/kg (p

Neurally adjusted ventilatory assist (NAVA) delivers assist in proportion to the patient's respiratory drive as reflected by the diaphragm electrical activity (EAdi). We examined to what extent NAVA can unload inspiratory muscles, and whether unloading is sustainable when implementing a NAVA level identified as adequate (NAVAal) during a titration procedure.Fifteen adult, critically ill patients with a Pao(2)/fraction of inspired oxygen (Fio(2)) ratio300 mm Hg were studied. NAVAal was identified based on the change from a steep increase to a less steep increase in airway pressure (Paw) and tidal volume (Vt) in response to systematically increasing the NAVA level from low (NAVAlow) to high (NAVAhigh). NAVAal was implemented for 3 h.At NAVAal, the median esophageal pressure time product (PTPes) and EAdi values were reduced by 47% of NAVAlow (quartiles, 16 to 69% of NAVAlow) and 18% of NAVAlow (quartiles, 15 to 26% of NAVAlow), respectively. At NAVAhigh, PTPes and EAdi values were reduced by 74% of NAVAlow (quartiles, 56 to 86% of NAVAlow) and 36% of NAVAlow (quartiles, 21 to 51% of NAVAlow; por = 0.005 for all). Parameters during 3 h on NAVAal were not different from parameters during titration at NAVAal, and were as follows: Vt, 5.9 mL/kg predicted body weight (PBW) [quartiles, 5.4 to 7.2 mL/kg PBW]; respiratory rate (RR), 29 breaths/min (quartiles, 22 to 33 breaths/min); mean inspiratory Paw, 16 cm H(2)O (quartiles, 13 to 20 cm H(2)O); PTPes, 45% of NAVAlow (quartiles, 28 to 57% of NAVAlow); and EAdi, 76% of NAVAlow (quartiles, 63 to 89% of NAVAlow). Pao(2)/Fio(2) ratio, Paco(2), and cardiac performance during NAVAal were unchanged, while Paw and Vt were lower, and RR was higher when compared to conventional ventilation before implementing NAVAal.Systematically increasing the NAVA level reduces respiratory drive, unloads respiratory muscles, and offers a method to determine an assist level that results in sustained unloading, low Vt, and stable cardiopulmonary function when implemented for 3 h.

BACKGROUND: To test the hypothesis that reduced responsiveness to adrenocorticotropin (ACTH) stimulation before elective major abdominal surgery is associated with an increased incidence of postoperative complications. METHODS: A low-dose (1 microg) ACTH test was performed the day before surgery, during the operation, on the first postoperative day, and before discharge from the hospital in 77 patients undergoing major abdominal surgery (age 62 [47;69] yrs [median, quartiles]; 30 female). Thirty-one patients undergoing minor, non-abdominal surgery (mostly inguinal hernia repair) (age 57 [40;66] yrs; 14 female) served as controls with minor surgical stress. A stimulated plasma cortisol concentration >or=500 nmol/l or an increment of >or=200 nmol/l in response to 1 microg ACTH was defined as normal. Scores for surgical stress and comprehensive risk, postoperative complications, and length of hospital stay (LOS) were assessed. RESULTS: On the day before major abdominal surgery, basal and stimulated plasma cortisol were 242 (165;299) nmol/l and 497 (404;568) nmol/l, respectively. Eighteen (23%) patients had an abnormal ACTH test, and 7 of these (39%) had complications versus 25 (42%) of the 59 patients with normal ACTH tests (P = .992). Surgical stress, comprehensive risk, and intra- and postoperative basal cortisol levels were higher and the response to ACTH stimulation smaller in patients with major abdominal compared to minor surgery. The peri-operative course of ACTH responses was not associated with complications or LOS in abdominal surgery patients. CONCLUSION: In patients scheduled for abdominal surgery, pre-operatively reduced adrenal response to stimulation with 1 microg ACTH is common but not associated with postoperative complications.

This study evaluated the response to increasing levels of neurally adjusted ventilatory assist (NAVA), a mode converting electrical activity of the diaphragm (EAdi) into pressure, regulated by a proportionality constant called the NAVA level. Fourteen rabbits were studied during baseline, resistive loading and ramp increases of the NAVA level. EAdi, airway (Paw) and esophageal pressure (Pes), Pes pressure time product (PTPes), breathing pattern, and blood gases were measured. Resistive loading increased PTPes and EAdi. P(a)(CO)(2) increased with high load but not during low load. Increasing NAVA levels increased Paw until a breakpoint where the Paw increase was reduced despite increasing NAVA level. At this breakpoint, Pes, PTPes, EAdi, and P(a)(CO)(2) were similar to baseline. Further increase of the NAVA level reduced Pes, PTPes and EAdi without changes in ventilation. In conclusion, observing the trend in Paw during a ramp increase of the NAVA level allows determination of a level where the inspiratory effort matches unloaded conditions.

Objective Patient–ventilator synchrony during non-invasive pressure support ventilation with the helmet device is often compromised when conventional pneumatic triggering and cycling-off were used. A possible solution to this shortcoming is to replace the pneumatic triggering with neural triggering and cycling-off—using the diaphragm electrical activity (EAdi). This signal is insensitive to leaks and to the compliance of the ventilator circuit. Design Randomized, single-blinded, experimental study. Setting University Hospital. Participants and subjects Seven healthy human volunteers. Interventions Pneumatic triggering and cycling-off were compared to neural triggering and cycling-off during NIV delivered with the helmet. Measurements and results Triggering and cycling-off delays, wasted efforts, and breathing comfort were determined during restricted breathing efforts (

OBJECTIVE: Neurally adjusted ventilatory assist uses the electrical activity of the diaphragm (EAdi)-a pneumatically-independent signal-to control the timing and pressure of the ventilation delivered, and should not be affected by leaks. The aim of this study was to evaluate whether NAVA can deliver assist in synchrony and proportionally to EAdi after extubation, with a leaky non-invasive interface. DESIGN AND SETTING: Prospective, controlled experimental study in an animal laboratory. ANIMALS: Ten rabbits, anesthetized, mechanically ventilated. INTERVENTIONS: Following lung injury, the following was performed in sequential order: (1) NAVA delivered via oral endotracheal tube with PEEP; (2) same as (1) without PEEP; (3) non-invasive NAVA at unchanged NAVA level and no PEEP via a single nasal prong; (4) no assist; (5) non-invasive NAVA at progressively increasing NAVA levels. MEASUREMENTS AND RESULTS: EAdi, esophageal pressure, blood gases and hemodynamics were measured during each condition. For the same NAVA level, the mean delivered pressure above PEEP increased from 3.9[Symbol: see text]+/-[Symbol: see text]1.4[Symbol: see text]cmH(2)O (intubated) to 7.5[Symbol: see text]+/-[Symbol: see text]3.8[Symbol: see text]cmH(2)O (non-invasive) (p[Symbol: see text]

With increasing pressure support ventilation (PSV), a form of pneumatically triggered ventilation, there can be an increase in wasted inspiratory efforts (neural inspiratory efforts that fail to trigger the ventilator). With neurally adjusted ventilatory assist (NAVA), a mode of ventilation controlled by the electrical activity of the diaphragm (EAdi), synchrony should be maintained at high levels of assist. The aim of this study was to evaluate the response to increasing levels of PSV and NAVA on synchrony and diaphragm unloading in lung-injured rabbits. Animals were ventilated on PSV or NAVA in random order, each at three levels. We measured neural and ventilator respiratory rates, EAdi, transdiaphragmatic pressure (Pdi), and tidal volume (VT). At low PSV, 95% of neural efforts were triggered, compared with high PSV, where only 66% of the neural efforts were triggered. During NAVA, all neural efforts were triggered, regardless of level. Increasing NAVA levels reduced EAdi and Pdi-time products by 48% (p < 0.05) and 66% (p < 0.05). In contrast, increasing PSV did not reduce the diaphragm electrical activity-time product and increased the transdiaphragmatic pressure-time product (p < 0.05) due to the increased wasted efforts. We conclude that synchrony with the ventilator is an important determinant for diaphragm unloading.

A 46-yr-old man developed severe hypoxemia, pulmonary infiltrates, and an acute decrease in his leukocyte count shortly after transfusion of fresh-frozen plasma (FFP) during recovery from cardiac surgery. Cardiogenic pulmonary edema was excluded. Granulocyte-reactive and agglutinating alloantibodies were detected in the serum of the fresh-frozen plasma donor. The cross-match with the patient's granulocytes revealed antibodies specific for HLA class I. Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, under-recognized and under-reported complication of transfusion. Conservative transfusion strategies and preclusion of the implicated blood donors with granulocyte-reactive antibodies from future blood donation may prevent TRALI and could save lives.Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, probably under-recognized and under-reported complication of transfusing blood products. Conservative transfusion strategies and preclusion of the implicated blood donors with granulocyte-reactive antibodies from future blood donation may prevent TRALI and potentially save lives.

Percutaneous dilatational tracheostomy (PDT) is a frequently conducted procedure in critically ill patients. Bronchoscopic guidance of PDT is generally recommended to minimize the risk of unintentional tracheal injury. We present a case of tracheal tear and tension pneumothorax, a rare but potentially life-threatening complication, during continuously bronchoscopy-guided PDT. Sealing the large tracheal air fistula with the cuff of an endotracheal tube helped bridge time to definitive surgical repair in our patient. Bronchoscopic guidance may minimize, but cannot completely eliminate, the risk of tracheal injury during PDT.

Objective: To assess the effects of low hepatosplanchnic blood flow on regional blood flow control and oxygenation. Design: Three randomized, controlled animal experiments. Setting: Two university experimental research laboratories. Subjects: Pigs of either gender. Interventions: Isolated abdominal blood flow reduction: An extracorporeal shunt with reservoir and roller pump was inserted between proximal and distal aorta in 11 pigs. Abdominal aortic blood flow was reduced by 50% by activating the shunt. Mesenteric ischemia: In seven pigs, superior mesenteric arterial flow was reduced to 4 mL.kg -1 .min -1 for 4 hrs. Cardiac tamponade: In 12 pigs, aortic blood flow was reduced by cardiac tamponade to 50 mL (moderate tamponade) and further to 30 mL.kg -1 .min -1 (severe tamponade) for 1 hr each. In each experimental condition, the same number of control animals was used. Measurements and Main Results: Abdominal blood flow reduction, acute mesenteric ischemia, and moderate tamponade resulted in a portal venous flow (Q PV ) reduction to 51 ± 23%, 52 ± 18%, and 61 ± 25% (mean ± so) of baseline flow, respectively. During abdominal blood flow reduction, Q PV and hepatic arterial flow (Q HA ) decreased proportionally, whereas in moderate tamponade and acute mesenteric ischemia Q PV reduction was associated with an increase in Q HA of 30 ± 39% and 102 ± 108%, respectively (p =.001 and.018). Prolonged mesenteric ischemia restored total hepatic blood flow (Q liver ) completely. During all conditions, decreasing mesenteric oxygen consumption was partly prevented by increased mesenteric oxygen extraction (p < .001 for all conditions). In contrast, decreasing hepatic oxygen delivery was associated with increased oxygen extraction in tamponade (p =.009) but not in abdominal blood flow reduction. Conclusions: Blood flow redistribution can restore Q liver totally when mesenteric blood flow is reduced selectively, partially when cardiac output is reduced, and not at all during abdominal blood flow reduction. Since hepatic oxygen extraction does not increase in abdominal blood flow reduction, hepatic oxygenation is at risk in this condition.

UNLABELLED Recruitment maneuvers (RM) are advocated as a complement to mechanical ventilation during anesthesia and in acute lung injury. However, they produce high intrathoracic pressures and volumes that may compromise hemodynamics. Our aim was to analyze the effect of a RM on hemodynamics in 10 anesthetized pigs. We assessed carotid, pulmonary, femoral, and hepatic arterial pressures, hepatic and portal venous pressures, total splanchnic (celiac trunk + superior mesenteric artery), hepatic, splenic, renal, and carotid arterial flows, and portal venous flow. We recorded hemodynamics, respiratory mechanics and blood gases before and at 8 min after RM (sustained inflation to 40 cm H(2)O of airway pressure lasting 20 s). Hemodynamics were also measured during RM, and at 1, 3, and 5 min after RM. All flows (P = 0.030) and arterial pressures (P < or = 0.048) decreased during RM, whereas venous pressures increased (P = 0.030). Flows and pressures returned to 75%-109% of baseline immediately after RM. Total splanchnic, renal and portal flows remained decreased at 8 min after RM (P < or = 0.042). Oxygenation did not change, and respiratory mechanics improved after the RM. RM produced a marked, though transitory, impairment of blood flow in all studied vessels. Despite prompt partial recovery, total splanchnic circulation remained reduced at 8 min after RM. This residual decrease may present a risk in conditions with markedly compromised circulatory reserves. IMPLICATIONS Recruitment maneuvers (RM) produce high intrathoracic pressures and volumes that may compromise hemodynamics. We found a marked transient impairment of hemodynamics during a RM in 10 anesthetized pigs. At 8 min after RM, blood flow remained reduced in the celiac trunk, superior mesenteric, and renal arteries, as well as in the portal vein. This residual decrease may present a risk in conditions with markedly compromised circulatory reserves.

Objective: To compare two methods of assessing a change in stroke volume in response to fluid challenge: esophageal Doppler and thermodilution with the pulmonary artery catheter. Design: Prospective study. Setting: Department of Intensive Care of a university medical center. Patients: 19 adult patients, intubated and sedated, with a pulmonary catheter and a clinical indication for a fluid challenge. Interventions: Two examiners independently assessed the effect of a fluid challenge on stroke volume and cardiac output with esophageal Doppler. Thermodilution performed by an independent clinician was used as the reference. Between-method variation and interobserver variability of the Doppler method were assessed. Measurements and results: There were no differences in stroke volume and cardiac output before volume challenge when measured with either of the two methods or by the two examiners using the esophageal Doppler. Despite a small bias between the methods and the two examiners using the esophageal Doppler (overall bias for cardiac output 0.3l/min), the precision was poor (1.8l/min). Conclusions: The esophageal Doppler method is a non-invasive alternative to the pulmonary artery catheter for the assessment of stroke volume in critically ill patients. Measurement of stroke volume response to fluid challenge using esophageal Doppler shows substantial interobserver variability. Despite the poor precision between methods and investigators, similar directional changes in stroke volume can be measured

Objective: pCO2 gradients are used for the assessment of splanchnic regional and local mucosal blood flow changes in experimental and clinical research. pCO2 gradients may not parallel blood flow changes because of concomitant changes in metabolism, hemoglobin, temperature, and the Haldane effect. Design and setting: A randomized, controlled animal experiment in a university experimental research laboratory. Interventions: An extracorporeal shunt with reservoir and roller pump was inserted between the proximal and the distal abdominal aorta in 16 pigs. In animals randomized to the low-flow group (n=8) splanchnic perfusion was reduced by running the roller pump. At baseline and after 45min of stable shunt flow superior mesenteric artery, celiac trunk, spleen artery, and portal vein blood flows and regional venous-arterial and jejunal and gastric mucosal-arterial pCO2 gradients were measured, and the respective regional O2 consumption rates (VO2) calculated. Measurements and results: In the low-flow group all regional blood flows and the associated VO2 decreased to roughly 50% of baseline values, and hemoglobin decreased from 7.3 (4.4-9.6) g/dl to 5.7 (4.1-8.9) g/dl. Decreasing regional blood flows were consistently associated with increasing regional and mucosal pCO2 gradients. Conclusions: During isolated reduction in abdominal aortic blood flow there is no preferential distribution to any splanchnic vascular bed and changes in regional pCO2 gradients reflect consistently the associated blood blow changes

Introduction The clinical relevance of preclinical sepsis research has been questioned [1]. This may in part be the result of varying degrees of experimental infl ammatory insults. The objective of this study was to quantify infl ammation based on plasma TNFa levels after exposure to two diff erent bacterial loads and after diff erent lengths of bacterial incubation in the peritoneal cavity. Methods We retrospectively evaluated plasma TNFa concentrations measured before and 24 hours after fecal peritonitis induced by 1 g/ kg autologous feces (16 anesthetized pigs median weight: 40.0 kg) and after 6 12 and 24 hours of fecal peritonitis induced with 2 g/kg autologous feces (24 anesthetized pigs (n = 8/group); median weight: 41.0 kg). All animals were resuscitated with fl uids norepinephrine and antibiotics and were mechanically ventilated according to standardized protocols. Diff erences along time after fecal peritonitis induced with 2 g/kg feces were assessed by ANOVA for repeated measures. Comparison between the two models (1 g/kg vs. 2 g/kg) after 24 hours of peritonitis was performed with an independent t test. Results TNFa increased from baseline to 6 12 and 24 hours of peritonitis induced with 2 g/kg feces (P

Introduction Sepsis-induced myopathy and critical illness myopathy (CIM) are possible causes of muscle weakness in intensive care patients. They have been attributed to muscle membrane dysfunction. The aim of this study was to investigate membrane properties in the early stage of experimental sepsis by evaluating muscle excitability. Methods In total, 20 anaesthetized and mechanically ventilated pigs were randomized to either faecal peritonitis (n = 10) or to non-septic controls (n = 10). Resuscitation with fluids and vasoactive drugs was started 3 hours after peritonitis induction. Muscle membrane properties were investigated by measuring muscle velocity recovery cycles before induction of peritonitis as well as 6, 18 and 27 hours thereafter. Muscle relative refractory period (MRRP) and early supernormality (ESN) were assessed. Results Peritonitis lasting 27 hours was associated with an increase of MRRP by 28% from 2.38 ± 0.18 ms (mean ± SD) to 3.47 ± 1.79 ms (P

Muscle weakness and atrophy due to critical illness polyneuromyopathy (CIPM) is common in long-stay intensive care patients. Recent nerve excitability studies suggest that the recovery cycle after a single supramaximal stimulus provides useful information about axonal membrane potential and ion channel function in neuropathies. We previously found that critical illness polyneuropathy is associated with nerve depolarization, and that this depolarization is strongly correlated with serum potassium in patients with renal failure [1]. We have adapted this method to human muscle fibres, by measuring the changes in conduction velocity of muscle fibres [2]. The muscle relative refractory period (RRP) increases and supernormality (SN) decreases in ischaemia, suggesting that these measures may be indicators of membrane potential also in the muscle [2]. The aim of this study was to evaluate muscle RRP and SN in patients with CIPM.

Neurally adjusted ventilatory assistance (NAVA) delivers pressure (Paw) in proportion to the electrical activity of the diaphragm (EAdi). It is not known whether EAdi adequately reflects the respiratory drive in patients with critical illness polyneuromyopathy (CIPM) and would be sufficient to deliver assistance using NAVA.

Introduction Experimental and clinical studies have shown a reduction in intrapulmonary shunt with spontaneous breathing during airway pressure release ventilation (APRV) in acute lung injury. This reduction was related to reduced atelectasis and increased aeration. We hypothesized that spontaneous breathing will result in better ventilation and aeration of dependent lung areas and in less cyclic collapse during the tidal breath. Methods In this randomized controlled experimental trial, 22 pigs with oleic-acid-induced lung injury were randomly assigned to receive APRV with or without spontaneous breathing at comparable airway pressures. Four hours after randomization, dynamic computed tomography scans of the lung were obtained in an apical slice and in a juxtadiaphragmatic transverse slice. Analyses of regional attenuation were performed separately in nondependent and dependent halves of the lungs on end-expiratory scans and end-inspiratory scans. Tidal changes were assessed as differences between inspiration and expiration of the mechanical breaths. Results Whereas no differences were observed in the apical slices, spontaneous breathing resulted in improved tidal ventilation of dependent lung regions (P < 0.05) and less cyclic collapse (P < 0.05) in the juxtadiaphragmatic slices. In addition, with spontaneous breathing, the end-expiratory aeration increased and nonaerated tissue decreased in dependent lung regions close to the diaphragm (P < 0.05 for the interaction ventilator mode and lung region). Conclusion Spontaneous breathing during APRV redistributes ventilation and aeration to dependent, usually well-perfused, lung regions close to the diaphragm, and may thereby contribute to improved arterial oxygenation. Spontaneous breathing also counters cyclic collapse, which is a risk factor for ventilation-associated lung injury.

We summarize all original research in the field of respirology and critical care published in 2003 and 2004 in Critical Care. Articles were grouped into the following categories to facilitate a rapid overview: pathophysiology, therapeutic approaches, and outcome in acute lung injury and acute respiratory distress syndrome; hypoxic pulmonary arterial hypertension; mechanical ventilation; liberation from mechanical ventilation and tracheostomy; ventilator-associated pneumonia; multidrug-resistant infections; pleural effusion; sedation and analgesia; asthma; and techniques and monitoring.