Prolonged bilateral reactive miosis as a symptom of severe insulin intoxication.

BACKGROUND: Miosis occurs following exposure to toxins that decrease the sympathomimetic tone, increase the cholinergic tone, or exert sedative-hypnotic effects, but has not been reported in insulin poisoning. CASE REPORT: A 64-year- old woman without co-morbidities was found unconscious next to an empty insulin pen. Her Glasgow Coma Scale was 3 with absent reflexes, bilateral reactive miosis, and injection marks across the abdominal wall. The patient was endotracheally intubated, mechanically ventilated, and transferred to this hospital. At admission, the blood glucose level was 34 mg/dL. Glasgow Coma Scale remained at 3, with persistent bilateral reactive miosis. The toxicology screening was negative for ethanol, barbiturates, tricyclic antidepressants, phenothiazines, amphetamines, cannabinoids, salicylates, acetaminophen, and cocaine. Cranial computed tomography with angiography and magnetic resonance imaging (MRI) did not show any structural brain lesions. Intravenous glucose was continued at 6-14 g/h for 3 days. On repeated neurological examinations, the patient remained deeply comatose, with partial loss of cranial nerve function. Bilateral reactive miosis persisted for 4 days. From day 5 on, the patient awoke progressively. At discharge, the patient was fully alert and orientated, without a focal neurological deficit. CONCLUSIONS: Prolonged bilateral reactive miosis can be a clinical symptom accompanying metabolic encephalopathy in severe insulin poisoning. Functional impairment of the pons due to relative hypoperfusion during hypoglycemia may serve as a reasonable pathophysiologic explanation for this phenomenon.

Histologic pathologies of the myocardium in septic shock: a prospective observational study.

Myocardial depression in septic shock is well known, but its pathophysiological genesis is incompletely understood. To assess the incidence and extent of stress-induced histologic myocardial alterations in septic shock, a prospective, observational, combined clinical and postmortem study was conducted, and 20 patients dying from septic shock were included. Exclusion criteria were younger than 18 years, pregnancy, open heart surgery or cardiopulmonary resuscitation, acute neurologic diseases, pheochromocytoma, and forensic autopsy. A systematic macropathologic evaluation was performed. Nine predefined heart sections were histologically screened for myocytolysis, interstitial fibrosis, contraction band necrosis, mononuclear infiltrates, interstitial edema, and tissue hemorrhage. Stress-induced pathologies were found in 90% to 100% of patients in all heart sections (myocytolysis, 100%; interstitial fibrosis, 100%; contraction band necrosis, 95%; mononuclear infiltrates, 90%; interstitial edema, 90%; tissue hemorrhage, 30%). The incidence and extent of contraction band necrosis, mononuclear infiltrates, and myocytolysis did not differ between sexes; patients with or without chronic ß-blocker, calcium antagonist, and/or statin premedication; or between the binary use of different catecholamine agents (all comparisons P > 0.05). The maximum epinephrine dose correlated with the overall extent of mononuclear infiltrates (Spearman-Rho, r = 0.704; P = 0.05) and myocytolysis (Spearman-Rho, r = 0.933; P = 0.001). Maximum norepinephrine doses correlated with the extent of mononuclear infiltrates in the left ventricular anterior wall (Spearman-Rho, r = 0.519; P = 0.02). The total duration of catecholamine therapy was correlated with the extent of mononuclear infiltrates in the apex (Spearman-Rho, r = 0.571; P = 0.009) and right atrium (Spearman-Rho, r = 0.535; P = 0.02). In conclusion, our results suggest that histologic lesions potentially indicative of stress-induced cardiotoxicity can be observed in most patients dying from septic shock.

Haemodynamic variables and functional outcome in hypothermic patients following out-of-hospital cardiac arrest.

AIM OF THE STUDY: To evaluate the association between haemodynamic variables during the first 24h after intensive care unit (ICU) admission and neurological outcome in out-of-hospital cardiac arrest (OHCA) victims undergoing therapeutic hypothermia. METHODS: In a multi-disciplinary ICU, records were reviewed for comatose OHCA patients undergoing therapeutic hypothermia. The hourly variable time integral of haemodynamic variables during the first 24h after admission was calculated. Neurologic outcome was assessed at day 28 and graded as favourable or adverse based on the Cerebral Performance Category of 1-2 and 3-5. Bi- and multivariate regression models adjusted for confounding variables were used to evaluate the association between haemodynamic variables and functional outcome. RESULTS: 67/134 patients (50%) were classified as having favourable outcome. Patients with adverse outcome had a higher mean heart rate (73 [62-86] vs. 66 [60-78]bpm; p=0.04) and received noradrenaline more frequently (n=17 [25.4%] vs. n=9 [6%]; p=0.02) and at a higher dosage (128 [56-1004] vs. 13 [2-162] µgh(-1); p=0.03) than patients with favourable outcome. The mean perfusion pressure (mean arterial blood pressure minus central venous blood pressure) (OR=1.001, 95% CI =1-1.003; p=0.04) and cardiac index time integral (OR=1.055, 95% CI=1.003-1.109; p=0.04) were independently associated with adverse outcome at day 28. CONCLUSION: Mean perfusion pressure and cardiac index during the first 24h after ICU admission were weakly associated with neurological outcome in an OHCA population undergoing therapeutic hypothermia. Further studies need to elucidate whether norepinephrine-induced increases in perfusion pressure and cardiac index may contribute to adverse neurologic outcome following OHCA.

Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study.

PURPOSE: To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure. METHODS: The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h. RESULTS: Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8-57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08-2.77; p = 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1-1.01; p = 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (p < 0.001) and mechanical ventilation (p < 0.001) for longer and had longer intensive care unit stays (p < 0.001) and greater mortality (25.9 vs. 1.7 %; p < 0.001) than patients who did not. CONCLUSIONS: Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.

Concomitant arginine-vasopressin and hydrocortisone therapy in severe septic shock: association with mortality.

PURPOSE: To evaluate the association between concomitant arginine-vasopressin (AVP)/hydrocortisone therapy and mortality in severe septic shock patients. METHODS: This retrospective study included severe septic shock patients treated with supplementary AVP. To test the association between concomitant AVP/hydrocortisone use and mortality, a multivariate regression and Cox model (adjusted for admission year, initial AVP dosage and the Sepsis-related Organ Failure Assessment score before AVP) as well as a propensity score-based analysis were used. In both models, intensive care unit (ICU) and 28-day mortality served as outcome variables. RESULTS: One hundred fifty-nine patients were included. Hydrocortisone was administered to 76 (47.8%) at a median daily dosage of 300 (200-300) mg. In the multivariate logistic regression model, concomitant use of AVP and hydrocortisone was associated with a trend towards lower ICU (OR, 0.51; CI 95%, 0.24-1.08; p = 0.08) and 28-day (HR, 0.69; CI 95%, 0.43-1.08; p = 0.11) mortality. The probability of survival at day 28, as predicted by the regression model, was significantly higher in patients treated with concomitant AVP and hydrocortisone compared to those receiving AVP without hydrocortisone (p = 0.001). In a propensity score-based analysis, ICU (45 vs. 65%; OR, 0.69; CI 95% 0.38-1.26; p = 0.23) and 28-day mortality (35.5 vs. 55%; OR, 0.59; CI 95%, 0.27-1.29; p = 0.18) was not different between patients treated with (n = 40) or without concomitant hydrocortisone (n = 40). CONCLUSION: Concomitant AVP and hydrocortisone therapy may be associated with a survival benefit in septic shock. An adequately powered, randomised controlled trial appears warranted to confirm these preliminary, hypothesis-generating results.

Suctioning via the tube during endotracheal intubation in a model of severe upper airway haemorrhage: is there an advantage vs. suctioning with a separate catheter?

INTRODUCTION: In a model of severe simulated upper airway haemorrhage, we compared two techniques of performing endotracheal intubation: (1) suctioning via the endotracheal tube during laryngoscopy with subsequently advancing the endotracheal tube, and (2) the standard intubation strategy with performing laryngoscopy, and performing suction with subsequently advancing the endotracheal tube. METHODS: Forty-one emergency medical technicians intubated the trachea of a manikin with severe simulated airway haemorrhage using each technique in random order. RESULTS: There was no significant difference in the number of oesophageal intubations between suctioning via the tube and the standard intubation strategy [8/41 (20%) vs. 6/41 (15%); P = 0.688], but suctioning via the endotracheal tube needed significantly more time [median (IQR, CI 95%): 42 (20, 39-60) vs. 33 (15, 35-48)s; P = 0.015]. CONCLUSIONS: Suctioning via the endotracheal tube showed no benefit regarding the number of oesophageal intubations and needed more time when compared to the standard intubation strategy.

Current approach to the haemodynamic management of septic shock patients in European intensive care units: a cross-sectional, self-reported questionnaire-based survey.

BACKGROUND AND OBJECTIVE: The aim of this survey was to investigate clinicians' current approach to the haemodynamic management and resuscitation endpoints in septic shock. METHODS: This cross-sectional, self-reported questionnaire-based survey was sent to the clinical director of selected ICUs in 16 European countries. The questionnaire consisted of two parts and 25 questions. The first part retrieved general information on the hospital and ICU, and the second part of the questionnaire collected detailed information on the approach to haemodynamic management of septic shock. RESULTS: Of 481 clinicians invited to participate, 237 (49.3%) responded. Ninety-two questionnaires were excluded because of more than 20% missing responses, rendering 145 (30.1%) for statistical analysis. Administration of albumin (P = 0.007), gelatine preparations (P = 0.002), Ringer's solution (P = 0.02) and isotonic saline (P = 0.001) for fluid resuscitation varied between respondents from different countries. Further differences between respondents from different countries were observed for the choice of the first-line inotropic drug (P < 0.001), use of supplementary vasopressin (P = 0.02), supplementary fludrocortisone (P = 0.05) and measurement of cardiac output with the transpulmonary thermodilution (P = 0.001), lithium dilution (P = 0.004) and oesophageal Doppler (P = 0.005) technique. Mean arterial blood pressure (87%), central venous oxygen saturation (65%), central venous pressure (59%), systolic arterial blood pressure (48%), mixed venous oxygen saturation (42%) and cardiac index (42%) were the six haemodynamic variables most commonly claimed to be used as resuscitation endpoints. CONCLUSION: The current approach to the haemodynamic management of septic shock patients in a selected cohort of European ICU clinicians is in agreement with the Surviving Sepsis Campaign guidelines with the exception of the haemodynamic goals.

Automated emergency ventilation devices in a simulated unprotected airway.

BACKGROUND: Automated ventilation devices are becoming more popular for emergency ventilation, but there is still not much experience concerning the optimal ventilation mode. METHODS: In a bench model representing a non-intubated patient in respiratory and cardiac arrest, we compared a pressure-cycled with a time- and volume-cycled automated ventilation device in their completely automated modes. The main study endpoints were inspiratory time, respiratory rate, stomach inflation, and lung tidal volumes. RESULTS: The pressure-cycled device inspired for 6.7 s in the respiratory arrest setting (respiratory rate 5.6/min), and never reached its closing pressure in the cardiac arrest setting (respiratory rate 1 breath/min). The time- and volume-cycled device inspired in both settings for 1.7 s (respiratory rate 13 breaths/min). In the respiratory arrest setting, mask leakage was 620 ± 20 mL for the pressure-cycled device vs. 290 ± 10 mL for the time- and volume-cycled device (p < 0.0001); lung tidal volume was 1080 ± 50 mL vs. 490 ± 20 mL, respectively (p < 0.0001); and there was no stomach inflation for either device. In the cardiac arrest setting, pressure-cycled device mask leakage was 5460 ± 60 mL vs. 240 ± 20 mL (p < 0.0001) for the time- and volume-cycled device (p < 0.0001); stomach inflation was 13,100 ± 100 mL vs. 90 ± 10 mL, respectively (p < 0.0001); and lung tidal volume 740 ± 60 mL vs. 420 ± 20 mL, respectively (p < 0.0001). CONCLUSION: In a simulated respiratory arrest setting, ventilation with an automated pressure-cycled ventilation device resulted in lower respiratory frequency and larger tidal volumes compared to a time- and volume-cycled device. In a simulated cardiac arrest setting, ventilation with an automated pressure-cycled ventilation device, but not a time- and volume-cycled device, resulted in continuous gastric insufflation.

Early fish oil supplementation and organ failure in patients with septic shock from abdominal infections: a propensity-matched cohort study.

BACKGROUND: Fish oil (FO) has immunomodulating effects and may improve organ function and outcome in critically ill patients. This retrospective, propensity-matched cohort study investigates the effects of early intravenous FO supplementation on organ failure in patients with septic shock from abdominal infection. METHODS: A medical database was retrospectively searched for critically ill patients admitted because of septic shock from abdominal infection (n = 194). Demographic, clinical, and laboratory data; FO supplementation (10 g/d) (n = 42); rate, degree, and number of organ failures assessed by the Sequential Organ Failure Assessment (SOFA) score; and secondary outcome variables were recorded. A propensity score-based model was used to establish 2 comparable groups (FO, n = 29; control, n = 29). Mann-Whitney rank sum test, Fisher exact test, and logistic regression analyses were used to compare variables between groups. RESULTS: There were no differences in the rate of single organ failures, the maximum SOFA score (median [interquartile range (IQR)], 12 [8-15] vs 11 [9-14]; P = .99), or the number of organ failures (median [IQR], 2 [1-3] vs 2 [1-3]; P = .54] between patients receiving FO supplementation and those not receiving supplementation. There were no group differences in the maximum C-reactive protein levels (P = .1), duration of mechanical ventilation (P = .65) or hemofiltration (P = .21), intensive care unit-acquired infections, intensive care unit length of stay (P = .59), and intensive care unit (P = 1) or hospital mortality (P = 1). CONCLUSIONS: Early intravenous FO may not decrease the number and degree of organ failures in patients with septic shock from abdominal infection. Future trials are needed before FO supplementation in septic shock from abdominal infection can be recommended.

The association between body-mass index and patient outcome in septic shock: a retrospective cohort study.

BACKGROUND: It is unknown whether body-mass index (BMI) and commonly defined BMI categories are associated with mortality in patients with septic shock. METHODS: The database of a multidisciplinary intensive care unit (ICU) was retrospectively screened for adult patients with septic shock. BMI, demographic, clinical and laboratory variables together with outcome measures were collected in all patients. Subjects were categorized as follows: underweight, BMI < 18.5; normal weight, BMI 18.5-24.9; overweight, BMI 25-29.9; obesity, BMI >or= 30. Bivariate and multivariate logistic regression models were used to evaluate the association between BMI and outcome parameters. RESULTS: In total, 301 patients with septic shock were identified. BMI was bivariately associated with ICU mortality (OR 0.91; 95% CI 0.86-0.98; P = 0.007). There was no significant association between BMI and ICU mortality in the multivariate model but an increasing BMI tended to be associated with lower ICU mortality (OR 0.93; 95% CI 0.86-1.01; P = 0.09). Although overweight (OR 0.43; 95% CI 0.19-0.98; P = 0.04) and obese (OR 0.28; 95% CI 0.08-0.93; P = 0.04) patients had an independently lower risk of ICU death than those with normal weight, there was no difference in the risk of ICU death between normal weight and underweight patients (P = 0.22). A high BMI was independently associated with a lower frequency of acute delirium (P = 0.04) and a lower need for ICU re-admission (P = 0.001) but with a higher rate of ICU-acquired urinary tract infections (P = 0.02). CONCLUSIONS: BMI up to 50 does not appear to be associated with worse ICU and hospital mortality in patients with septic shock. In contrast, a high BMI may reduce the risk of death from septic shock.

How to protect the heart in septic shock: a hypothesis on the pathophysiology and treatment of septic heart failure.

Heart failure is a well-recognized manifestation of organ failure in sepsis and septic shock. The pathophysiology of septic heart failure is complex and currently believed to involve several mechanisms. So far, the contributory role of high plasma catecholamine levels has not been investigated. In this manuscript, we present a hypothesis suggesting that excessive catecholamine production and exogenous administration of catecholamines may relevantly contribute to the development of heart failure and cardiovascular collapse in patients suffering from septic shock. Substantially elevated plasma catecholamine levels were measured during critical illness and sepsis or septic shock. There is a growing body of clinical and experimental evidence demonstrating that high catecholamine plasma levels exert direct toxic effects on the heart. The pathophysiologic mechanisms involved in catecholamine-induced cardiomyocyte toxicity may involve a combination of inflammation, oxidative stress, and abnormal calcium handling resulting in myocardial stunning, apoptosis and necrosis. Clinical signs of catecholamine-induced heart failure can present with a wide range of symptoms reaching from subtle histological changes with preserved myocardial pump function to severe heart failure exhibiting a distinctive echocardiographic pattern which became known as "Takotsubo"-like cardiomyopathy or the left ventricular apical ballooning syndrome. In a medical intensive care unit patient population, presence of sepsis was the only variable associated with the development of left ventricular apical ballooning. Since several therapeutic interventions influence catecholamine plasma levels in septic shock patients, treatment strategies aiming at the reduction of endogenous or exogenous catecholamine exposure may protect the heart during septic shock and could facilitate patient survival.

Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial.

PURPOSE: To compare the effects of two arginine vasopressin (AVP) dose regimens on the hemodynamic response, catecholamine requirements, AVP plasma concentrations, organ function and adverse events in advanced vasodilatory shock. METHODS: In this prospective, controlled, open-label trial, patients with vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery requiring norepinephrine >0.6 microg/kg/min were randomized to receive a supplementary AVP infusion either at 0.033 IU/min (n = 25) or 0.067 IU/min (n = 25). The hemodynamic response, catecholamine doses, laboratory and organ function variables as well as adverse events (decrease in cardiac index or platelet count, increase in liver enzymes or bilirubin) were recorded before, 1, 12, 24 and 48 h after randomization. A linear mixed effects model was used for statistical analysis in order to account for drop-outs during the observation period. RESULTS: Heart rate and norepinephrine requirements decreased while MAP increased in both groups. Patients receiving AVP at 0.067 IU/min required less norepinephrine (P = 0.006) than those infused with AVP at 0.033 IU/min. Arterial lactate and base deficit decreased while arterial pH increased in both groups. During the observation period, AVP plasma levels increased in both groups (both P < 0.001), but were higher in the 0.067 IU/min group (P < 0.001) and in patients on concomitant hydrocortisone. The rate of adverse events and intensive care unit mortality was comparable between groups (0.033 IU/min, 52%; 0.067 IU/min, 52%; P = 1). CONCLUSIONS: A supplementary AVP infusion of 0.067 IU/min restores cardiovascular function in patients with advanced vasodilatory shock more effectively than AVP at 0.033 IU/min.

Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial.

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01). CONCLUSIONS: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

Hemodynamic variables and mortality in cardiogenic shock: a retrospective cohort study.

INTRODUCTION: Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality. METHODS: Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality. RESULTS: One-hundred and nineteen patients were included. Cardiac index (CI) (P = 0.01) and cardiac power index (CPI) (P = 0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops <3, 2.75 (both P = 0.02) and 2.5 (P = 0.03) L/min/m2 was associated with death but not that of CI drops <2 L/min/m2 or lower thresholds (all P > 0.05). The hourly time integral of CPI drops <0.5-0.8 W/m2 (all P = 0.04) was associated with 28-day mortality but not that of CPI drops <0.4 W/m2 or lower thresholds (all P > 0.05). CONCLUSIONS: During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock.

Ventilation strategies in the obstructed airway in a bench model simulating a nonintubated respiratory arrest patient.

BACKGROUND: The Smart Bag MO(R) is an adult flow-limited bag-valve device designed to reduce the risk of stomach inflation in an unprotected airway. Its properties in severe airway obstruction are as yet unknown. METHODS: In a bench model, we evaluated respiratory mechanics and delivered tidal volumes although ventilating at airway resistances of 4, 10, and 20 cm H(2)O . L(-1) . s(-1) once with a flow-limited bag-valve device and once with a standard bag-valve device to simulate a respiratory arrest patient with an unprotected airway. RESULTS: Inspiratory times were always longer with the flow-limited bag-valve device than with the standard bag-valve device. Lung tidal volume in the simulated unobstructed airway was 750 +/- 70 mL using the flow-limited bag-valve device versus 780 +/- 30 mL using the standard bag-valve device (n.s.); in the simulated medium obstructed airway it was 800 +/- 70 versus 850 +/- 20 mL (n.s.), and in the simulated severely obstructed airway it was 210 +/- 20 versus 170 +/- 10 mL (P < 0.01). Peak airway pressure in the simulated unobstructed airway was 15 +/- 2 cm H(2)O using the flow-limited bag-valve device versus 22 +/- 4 cm H(2)O using the standard bag-valve device (P < 0.01); in the simulated medium obstructed airway it was 22 +/- 1 versus 39 +/- 7 cm H(2)O (P < 0.01), and in the simulated severely obstructed airway it was 26 +/- 1 versus 61 +/- 3 cm H(2)O (P < 0.01). Stomach inflation in the simulated unobstructed airway was 0 mL/min using both bag-valve devices; in the simulated medium obstructed airway it was 0 mL/min for the flow-limited bag-valve device versus 200 +/- 20 mL/min for the standard bag-valve device (P < 0.01), and in the simulated severely obstructed airway it was 0 versus 1240 +/- 50 mL/min (P < 0.01). CONCLUSION: In a simulated severely obstructed unprotected airway, the use of a flow-limited bag-valve device resulted in longer inspiratory times, higher tidal volumes, lower inspiratory pressures, and no stomach inflation compared with a standard bag-valve device.

Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression.

INTRODUCTION: The multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function. METHODS: This retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 +/- 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis. RESULTS: Heart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 +/- 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P < 0.001). Cardiac index and cardiac power index remained unchanged whereas stroke volume index increased (P = 0.002). In two patients (5%), metoprolol was discontinued because of asymptomatic bradycardia. Norepinephrine and milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%. CONCLUSION: Low doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy and their influence on proinflammatory cytokines are warranted.

Use of an inspiratory impedance threshold valve during chest compressions without assisted ventilation may result in hypoxaemia.

INTRODUCTION: Although the concept of intermittent airway occlusion with the inspiratory impedance threshold valve (ITV) is a well-recognised strategy for improving efficiency of cardiopulmonary resuscitation (CPR), little is known about possible pulmonary side effects. METHODS: After a baseline chest CT-scan, 24 pigs with beating hearts undergoing apnoeic oxygenation received an injection of a contrast medium and were then assigned randomly to either active compression-decompression CPR with ITV (ACD ITV CPR), ACD CPR alone, or standard-CPR with ITV (standard-ITV CPR), or standard-CPR alone. After a maximum of 5 min of chest compressions or if oxygen saturation dropped below 70%, the experiment was stopped, haemodynamic variables and blood gas values were measured, and another CT-scan was performed; all animals underwent a 30 min recovery-period and a third subsequent CT-scan. RESULTS: At baseline arterial oxygen saturation by pulse oxymetry was 99% in all four groups; in both the ACD ITV CPR and the standard-ITV CPR groups, arterial oxygen saturation dropped below 70% within 126+/-9s, whereas chest compressions in all ACD CPR and standard-CPR pigs were performed over 5 min (P<0.001). Before stopping chest compressions arterial oxygen pressure decreased in the ACD ITV CPR group from 426+/-96 to 42+/-8 mmHg while it decreased in the ACD CPR group only from 415+/-116 to 197+/-127 mmHg (P<0.001 between groups); in the standard-ITV CPR group arterial oxygen partial pressure decreased from 427+/-109 to 34+/-5 mmHg while oxygen partial pressure decreased only from 467+/-44 to 144+/-98 mmHg in the standard-CPR group (P<0.004 between groups). After the second CT scan arterial oxygen partial pressure decreased further to 19+/-2 mmHg in the ACD ITV CPR versus 210+/-41 mmHg in the ACD CPR group; to 20+/-2 mmHg in the standard-ITV CPR versus 148+/-33 mmHg in the standard-CPR group. Lung-density values (Hounsfield units) were significantly higher in the ACD ITV CPR versus ACD CPR group (-134+/-54 versus -330+/-77) and standard-ITV CPR versus standard-CPR group (-98+/-50 versus -387+/-42). After a 30 min recovery-period, there were no significant differences in arterial oxygen partial pressure (ACD ITV CPR 275+/-110 mmHg versus ACD CPR 379+/-111 mmHg and standard-ITV CPR 265+/-138 mmHg versus standard CPR 367+/-55 mmHg). Furthermore, there were no differences in lung density values between groups after 30 min of recovery. CONCLUSION: In this animal model with a beating heart, intermittent airway obstruction through an ITV combined with apnoeic oxygenation and without active ventilation resulted in hypoxaemia due to transiently impaired lung function.