[Optimal oxygen administration-new evidence from treating COVID-19?] / Optimale Sauerstoffversorgung ­ neue Erkenntnisse aus der COVID-19-Therapie?

Oxygen is essential for energy production and thus for the survival of human cells. If oxygen delivery is disrupted due to illness, injury or changes in environmental factors, the human body is to a certain extent able to activate compensatory mechanisms to ensure adequate delivery of oxygen for the function and integrity of the cells and organ systems. If these compensatory mechanisms are exhausted or overloaded, there is a risk of functional failure of cells and organ systems. In clinical practice, it is often difficult to decide whether the body's own compensation mechanisms are still sufficient or whether more invasive therapy options and their side effects should be used to prevent organ damage. The aim of this review is to reiterate the basic physiological mechanisms of oxygen delivery to cells, to show how insufficient oxygen can be detected, and to highlight the current state of studies and guidelines on target oxygen levels. Although the coronavirus disease 2019 (COVID-19) pandemic has brought recent attention to the pathophysiology and therapeutic strategies of oxygenation disorders, little new knowledge regarding oxygen targets has emerged from this pandemic. Thus, the previously recommended oxygen target values remain unchanged.

Dexamethasone Improves Cardiovascular Outcomes in Critically Ill COVID-19, a Real World Scenario Multicenter Analysis.

BACKGROUND: Severe COVID-19 pneumonia requiring intensive care treatment remains a clinical challenge to date. Dexamethasone was reported as a promising treatment option, leading to a reduction of mortality rates in severe COVID-19 disease. However, the effect of dexamethasone treatment on cardiac injury and pulmonary embolism remains largely elusive. METHODS: In total 178 critically ill COVID-19 patients requiring intensive care treatment and mechanical ventilation were recruited in three European medical centres and included in the present retrospective study. One hundred thirteen patients (63.5%) were treated with dexamethasone for a median duration of 10 days (IQR 9-10). Sixty five patients (36.5%) constituted the non-dexamethasone control group. RESULTS: While peak inflammatory markers were reduced by dexamethasone treatment, the therapy also led to a significant reduction in peak troponin levels (231 vs. 700% indicated as relative to cut off value, p = 0.001). Similar, dexamethasone resulted in significantly decreased peak D-Dimer levels (2.16 mg/l vs. 6.14 mg/l, p = 0.002) reflected by a significant reduction in pulmonary embolism rate (4.4 vs. 20.0%, p = 0.001). The antithrombotic effect of dexamethasone treatment was also evident in the presence of therapeutic anticoagulation (pulmonary embolism rate: 6 vs. 34.4%, p < 0.001). Of note, no significant changes in baseline characteristics were observed between the dexamethasone and non-dexamethasone group. CONCLUSION: In severe COVID-19, anti-inflammatory effects of dexamethasone treatment seem to be associated with a significant reduction in myocardial injury. Similar, a significant decrease in pulmonary embolism, independent of anticoagulation, was evident, emphasizing the beneficial effect of dexamethasone treatment in severe COVID-19.

Red Cell Distribution Width Is Independently Associated with Mortality in Sepsis.

BACKGROUND: Mortality in sepsis remains high. Studies on small cohorts have shown that red cell distribution width (RDW) is associated with mortality. The aim of this study was to validate these findings in a large multicenter cohort. METHODS: We conducted this retrospective analysis of the multicenter eICU Collaborative Research Database in 16,423 septic patients. We split the cohort in patients with low (≤15%; n = 7,129) and high (>15%; n = 9,294) RDW. Univariable and multivariable multilevel logistic regressions were used to fit regression models for the binary primary outcome of hospital mortality and the secondary outcome intensive care unit (ICU) mortality with hospital unit as random effect. Optimal cutoffs were calculated using the Youden index. RESULTS: Patients with high RDW were more often older than 65 years (57% vs. 50%; p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) IV scores (69 vs. 60 pts.; p < 0.001). Both hospital (adjusted odds ratios [aOR] 1.18; 95% CI: 1.16-1.20; p < 0.001) and ICU mortality (aOR 1.16; 95% CI: 1.14-1.18; p < 0.001) were associated with RDW as a continuous variable. Patients with high RDW had a higher hospital mortality (20 vs. 9%; aOR 2.63; 95% CI: 2.38-2.90; p < 0.001). This finding persisted after multivariable adjustment (aOR 2.14; 95% CI: 1.93-2.37; p < 0.001) in a multilevel logistic regression analysis. The optimal RDW cutoff for the prediction of hospital mortality was 16%. CONCLUSION: We found an association of RDW with mortality in septic patients and propose an optimal cutoff value for risk stratification. In a combined model with lactate, RDW shows equivalent diagnostic performance to Sequential Organ Failure Assessment (SOFA) score and APACHE IV score.

Underweight but not overweight is associated with excess mortality in septic ICU patients.

BACKGROUND: Higher survival has been shown for overweight septic patients compared with normal or underweight patients in the past. This study aimed at investigating the management and outcome of septic ICU patients in different body mass index (BMI) categories in a large multicenter database. METHODS: In total, 16,612 patients of the eICU collaborative research database were included. Baseline characteristics and data on organ support were documented. Multilevel logistic regression analysis was performed to fit three sequential regression models for the binary primary outcome (ICU mortality) to evaluate the impact of the BMI categories: underweight (<18.5 kg/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2) and obesity (≥ 30 kg/m2). Data were adjusted for patient level characteristics (model 2) as well as management strategies (model 3). RESULTS: Management strategies were similar across BMI categories. Underweight patients evidenced higher rates of ICU mortality. This finding persisted after adjusting in model 2 (aOR 1.54, 95% CI 1.15-2.06; p = 0.004) and model 3 (aOR 1.57, 95%CI 1.16-2.12; p = 0.003). No differences were found regarding ICU mortality between normal and overweight patients (aOR 0.93, 95%CI 0.81-1.06; p = 0.29). Obese patients evidenced a lower risk of ICU mortality compared to normal weight, a finding which persisted across all models (model 2: aOR 0.83, 95%CI 0.69-0.99; p = 0.04; model 3: aOR 0.82, 95%CI 0.68-0.98; p = 0.03). The protective effect of obesity and the negative effect of underweight were significant in individuals > 65 years only. CONCLUSION: In this cohort, underweight was associated with a worse outcome, whereas obese patients evidenced lower mortality. Our analysis thus supports the thesis of the obesity paradox.

Higher Incidence of Stroke in Severe COVID-19 Is Not Associated With a Higher Burden of Arrhythmias: Comparison With Other Types of Severe Pneumonia.

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins. Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003; newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%). Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

ICU-Mortality in Old and Very Old Patients Suffering From Sepsis and Septic Shock.

Purpose: Old (>64 years) and very old (>79 years) intensive care patients with sepsis have a high mortality. In the very old, the value of critical care has been questioned. We aimed to compare the mortality, rates of organ support, and the length of stay in old vs. very old patients with sepsis and septic shock in intensive care. Methods: This analysis included 9,385 patients, from the multi-center eICU Collaborative Research Database, with sepsis; 6184 were old (aged 65-79 years), and 3,201 were very old patients (aged 80 years and older). A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of ICU mortality. A sensitivity analysis in septic shock patients (n = 1054) was also conducted. Results: In the very old patients, the median length of stay was shorter (50 ± 67 vs. 56 ± 72 h; p < 0.001), and the rate of a prolonged ICU stay was lower (>168 h; 9 vs. 12%; p < 0.001) than the old patients. The mortality from sepsis was higher in very old patients (13 vs. 11%; p = 0.005), and after multi-variable adjustment being very old was associated with higher odds for ICU mortality (aOR 1.32, 95% CI 1.09-1.59; p = 0.004). In patients with septic shock, mortality was also higher in the very old patients (38 vs. 36%; aOR 1.50, 95% CI 1.10-2.06; p = 0.01). Conclusion: Very old ICU-patients suffer from a slightly higher ICU mortality compared with old ICU-patients. However, despite the statistically significant differences in mortality, the clinical relevance of such minor differences seems to be negligible.

Pharmacokinetics and Antifungal Activity of Echinocandins in Ascites Fluid of Critically Ill Patients.

The pharmacokinetics and antifungal activity of the echinocandins anidulafungin (AFG), micafungin (MFG), and caspofungin (CAS) were assessed in ascites fluid and plasma of critically ill adults treated for suspected or proven invasive candidiasis. Ascites fluid was obtained from ascites drains or during paracentesis. The antifungal activity of the echinocandins in ascites fluid was assessed by incubation of Candida albicans and Candida glabrata at concentrations of 0.03 to 16.00 µg/ml. In addition, ascites fluid samples obtained from our study patients were inoculated with the same isolates and evaluated for fungal growth. These patient samples had to be spiked with echinocandins to restore the original concentrations because echinocandins had been lost during sterile filtration. In ascites fluid specimens of 29 patients, echinocandin concentrations were below the simultaneous plasma levels. Serial sampling in 20 patients revealed a slower rise and decline of echinocandin concentrations in ascites fluid than in plasma. Proliferation of C. albicans in ascites fluid was slower than in culture medium and growth of C. glabrata was lacking, even in the absence of antifungals. In CAS-spiked ascites fluid samples, fungal CFU counts moderately declined, whereas spiking with AFG or MFG had no relevant effect. In ascites fluid of our study patients, echinocandin concentrations achieved by therapeutic doses did not result in a consistent eradication of C. albicans or C. glabrata. Thus, therapeutic doses of AFG, MFG, or CAS may result in ascites fluid concentrations preventing relevant proliferation of C. albicans and C. glabrata, but do not warrant reliable eradication.

Myocardial injury in severe COVID-19 is similar to pneumonias of other origin: results from a multicentre study.

AIMS: COVID-19, a respiratory viral disease causing severe pneumonia, also affects the heart and other organs. Whether its cardiac involvement is a specific feature consisting of myocarditis, or simply due to microvascular injury and systemic inflammation, is yet unclear and presently debated. Because myocardial injury is also common in other kinds of pneumonias, we investigated and compared such occurrence in severe pneumonias due to COVID-19 and other causes. METHODS AND RESULTS: We analysed data from 156 critically ill patients requiring mechanical ventilation in four European tertiary hospitals, including all n = 76 COVID-19 patients with severe disease course requiring at least ventilatory support, matched to n = 76 from a retrospective consecutive patient cohort of severe pneumonias of other origin (matched for age, gender, and type of ventilator therapy). When compared to the non-COVID-19, mortality (COVID-19 = 38.2% vs. non-COVID-19 = 51.3%, P = 0.142) and impairment of systolic function were not significantly different. Surprisingly, myocardial injury was even more frequent in non-COVID-19 (96.4% vs. 78.1% P = 0.004). Although inflammatory activity [C-reactive protein (CRP) and interleukin-6] was indifferent, d-dimer and thromboembolic incidence (COVID-19 = 23.7% vs. non-COVID-19 = 5.3%, P = 0.002) driven by pulmonary embolism rates (COVID-19 = 17.1% vs. non-COVID-19 = 2.6%, P = 0.005) were higher. CONCLUSIONS: Myocardial injury was frequent in severe COVID-19 requiring mechanical ventilation, but still less frequent than in similarly severe pneumonias of other origin, indicating that cardiac involvement may not be a specific feature of COVID-19. While mortality was also similar, COVID-19 is characterized with increased thrombogenicity and high pulmonary embolism rates.

SARS-CoV-2: recommendations for treatment in intensive care medicine.

Coronavirus disease 2019 (COVID-19) progresses mildly in most of the cases; however, about 5% of the patients develop a severe acute respiratory distress syndrome (ARDS). Of all COVID-19 patients 3% need intensive care treatment, which becomes a great challenge for anesthesiology and intensive care medicine, medically, hygienically and for technical safety requirements. For these reasons, only experienced medical and nursing staff in the smallest grouping possible should be assigned. For these team members, a consistent use of personal protective equipment (PPE) is essential.Due to the immense medical challenges, the following treatment guidelines were developed by the ÖGARI (Österreichische Gesellschaft für Anästhesiologie, Reanimation und Intensivmedizin), FASIM (Federation of Austrian Societies of Intensive Care Medicine) and ÖGIAIN (Österreichische Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin).The recommendations given in this article are to be understood as short snapshots of the moment; all basic guidelines are works in progress and will be regularly updated as evidence levels, new study results and additional experience are gathered.

The Hen or the Egg: Impaired Alveolar Oxygen Diffusion and Acute High-altitude Illness?

Individuals ascending rapidly to altitudes >2500 m may develop symptoms of acute mountain sickness (AMS) within a few hours of arrival and/or high-altitude pulmonary edema (HAPE), which occurs typically during the first three days after reaching altitudes above 3000-3500 m. Both diseases have distinct pathologies, but both present with a pronounced decrease in oxygen saturation of hemoglobin in arterial blood (SO2). This raises the question of mechanisms impairing the diffusion of oxygen (O2) across the alveolar wall and whether the higher degree of hypoxemia is in causal relationship with developing the respective symptoms. In an attempt to answer these questions this article will review factors affecting alveolar gas diffusion, such as alveolar ventilation, the alveolar-to-arterial O2-gradient, and balance between filtration of fluid into the alveolar space and its clearance, and relate them to the respective disease. The resultant analysis reveals that in both AMS and HAPE the main pathophysiologic mechanisms are activated before aggravated decrease in SO2 occurs, indicating that impaired alveolar epithelial function and the resultant diffusion limitation for oxygen may rather be a consequence, not the primary cause, of these altitude-related illnesses.

Inhaled Budesonide Does Not Affect Hypoxic Pulmonary Vasoconstriction at 4559 Meters of Altitude.

Berger, Marc Moritz, Franziska Macholz, Peter Schmidt, Sebastian Fried, Tabea Perz, Daniel Dankl, Josef Niebauer, Peter Bärtsch, Heimo Mairbäurl, and Mahdi Sareban. Inhaled budesonide does not affect hypoxic pulmonary vasoconstriction at 4559 meters of altitude. High Alt Med Biol 19:52-59, 2018.-Oral intake of the corticosteroid dexamethasone has been shown to lower pulmonary artery pressure (PAP) and to prevent high-altitude pulmonary edema. This study tested whether inhalation of the corticosteroid budesonide attenuates PAP and right ventricular (RV) function after rapid ascent to 4559 m. In this prospective, randomized, double-blind, and placebo-controlled trial, 50 subjects were randomized into three groups to receive budesonide at 200 or 800 µg twice/day (n = 16 and 17, respectively) or placebo (n = 17). Inhalation was started 1 day before ascending from 1130 to 4559 m within 20 hours. Systolic PAP (SPAP) and RV function were assessed by transthoracic echocardiography at low altitude (423 m) and after 7, 20, 32, and 44 hours at 4559 m. Ascent to high altitude increased SPAP about 1.7-fold (p < 0.001), whereas RV function was preserved. There was no difference in SPAP and RV function between groups at low and high altitude (all p values >0.10). Capillary partial pressure of oxygen (PO2) and carbon dioxide as well as the alveolar to arterial PO2 difference were decreased at high altitude but not affected by budesonide. Prophylactic inhalation of budesonide does not attenuate high-altitude-induced pulmonary vasoconstriction and RV function after rapid ascent to 4559 m.

Remote ischemic preconditioning does not prevent acute mountain sickness after rapid ascent to 3,450 m.

Remote ischemic preconditioning (RIPC) has been shown to protect remote organs, such as the brain and the lung, from damage induced by subsequent hypoxia or ischemia. Acute mountain sickness (AMS) is a syndrome of nonspecific neurologic symptoms and in high-altitude pulmonary edema excessive hypoxic pulmonary vasoconstriction (HPV) plays a pivotal role. We hypothesized that RIPC protects the brain from AMS and attenuates the magnitude of HPV after rapid ascent to 3,450 m. Forty nonacclimatized volunteers were randomized into two groups. At low altitude (750 m) the RIPC group (n = 20) underwent 4 × 5 min of lower-limb ischemia (induced by inflation of bilateral thigh cuffs to 200 mmHg) followed by 5 min of reperfusion. The control group (n = 20) underwent a sham protocol (4 × 5 min of bilateral thigh cuff inflation to 20 mmHg). Thereafter, participants ascended to 3,450 m by train over 2 h and stayed there for 48 h. AMS was evaluated by the Lake Louise score (LLS) and the AMS-C score. Systolic pulmonary artery pressure (SPAP) was assessed by transthoracic Doppler echocardiography. RIPC had no effect on the overall incidence (RIPC: 35%, control: 35%, P = 1.0) and severity (RIPC vs. CONTROL: P = 0.496 for LLS; P = 0.320 for AMS-C score) of AMS. RIPC also had no significant effect on SPAP [maximum after 10 h at high altitude; RIPC: 33 (SD 8) mmHg; controls: 37 (SD 7) mmHg; P = 0.19]. This study indicates that RIPC, performed immediately before passive ascent to 3,450 m, does not attenuate AMS and the magnitude of high-altitude pulmonary hypertension.NEW & NOTEWORTHY Remote ischemic preconditioning (RIPC) has been reported to improve neurologic and pulmonary outcome following an acute ischemic or hypoxic insult, yet the effect of RIPC for protecting from high-altitude diseases remains to be determined. The present study shows that RIPC, performed immediately before passive ascent to 3,450 m, does not attenuate acute mountain sickness and the degree of high-altitude pulmonary hypertension. Therefore, RIPC cannot be recommended for prevention of high-altitude diseases.

Changes in peripheral perfusion relate to visceral organ perfusion in early septic shock: A pilot study.

PURPOSE: To correlate clinical indicators of peripheral perfusion with visceral organ vascular tone in 30 septic shock patients. MATERIALS AND METHODS: In a prospective pilot study, capillary refill time, the Mottling score, and peripheral temperature were determined within 24, 48, and 72 hours after intensive care unit admission. Simultaneously, pulsatility indices in the liver, spleen, kidneys, and intestines were measured by Doppler ultrasonography. Correlation analyses were calculated, applying an adjusted significance level (P< .0125) to correct for multiple testing. RESULTS: Significant relationships were observed between the pulsatility index of selected organs and the capillary refill time (intestines: r= 0.325, P= .007), and the Mottling score (kidneys: r= 0.396, P= .006), but not peripheral temperature (all r< 0.14, P> .05). An association over time was observed for the capillary refill time and pulsatility index of the liver (P= .04) and intestines (P= .03) as well as for the Mottling score and the kidneys' pulsatility index (P= .03), but not for peripheral temperature and any visceral organs' pulsatility index. CONCLUSIONS: Capillary refill time and skin mottling may be correlated with the pulsatility index, a sonographic surrogate of vascular tone, of visceral organs in early septic shock.

A Comparison of Web-Based with Traditional Classroom-Based Training of Lung Ultrasound for the Exclusion of Pneumothorax.

BACKGROUND: Lung ultrasound (LUS) is a well-established method that can exclude pneumothorax by demonstration of pleural sliding and the associated ultrasound artifacts. The positive diagnosis of pneumothorax is more difficult to obtain and relies on detection of the edge of a pneumothorax, called the "lung point." Yet, anesthesiologists are not widely taught these techniques, even though their patients are susceptible to pneumothorax either through trauma or as a result of central line placement or regional anesthesia techniques performed near the thorax. In anticipation of an increased training demand for LUS, efficient and scalable teaching methods should be developed. In this study, we compared the improvement in LUS skills after either Web-based or classroom-based training. We hypothesized that Web-based training would not be inferior to "traditional" classroom-based training beyond a noninferiority limit of 10% and that both would be superior to no training. Furthermore, we hypothesized that this short training session would lead to LUS skills that are similar to those of ultrasound-trained emergency medicine (EM) physicians. METHODS: After a pretest, anesthesiologists from 4 academic teaching hospitals were randomized to Web-based (group Web), classroom-based (group class), or no training (group control) and then completed a posttest. Groups Web and class returned for a retention test 4 weeks later. All 3 tests were similar, testing both practical and theoretical knowledge. EM physicians (group EM) performed the pretest only. Teaching for group class consisted of a standardized PowerPoint lecture conforming to the Consensus Conference on LUS followed by hands-on training. Group Web received a narrated video of the same PowerPoint presentation, followed by an online demonstration of LUS that also instructs the viewer to perform an LUS on himself using a clinically available ultrasound machine and submit smartphone snapshots of the resulting images as part of a portfolio system. Group Web received no other hands-on training. RESULTS: Groups Web, class, control, and EM contained 59, 59, 20, and 42 subjects. After training, overall test results of groups Web and class improved by a mean of 42.9% (±18.1% SD) and 39.2% (±19.2% SD), whereas the score of group control did not improve significantly. The test improvement of group Web was not inferior to group class. The posttest scores of groups Web and class were not significantly different from group EM. In comparison with the posttests, the retention test scores did not change significantly in either group. CONCLUSIONS: When training anesthesiologists to perform LUS for the exclusion of pneumothorax, we found that Web-based training was not inferior to traditional classroom-based training and was effective, leading to test scores that were similar to a group of clinicians experienced in LUS.

Influence of in-line microfilters on systemic inflammation in adult critically ill patients: a prospective, randomized, controlled open-label trial.

BACKGROUND: In critically ill children, in-line microfilters may reduce the incidence of the systemic inflammatory response syndrome (SIRS), the overall complication and organ dysfunction rate. No data on the use of in-line microfilters exist in critically ill adults. METHODS: In this prospective, randomized, controlled open-label study, we evaluated the influence of in-line microfilters on systemic immune activation in 504 critically ill adults with a central venous catheter in place and an expected length of stay in the intensive care unit >24 h. Patients were randomized to have in-line microfilters placed into all intravenous lines (intervention group) or usual care (control group). The primary endpoint was the number of intensive care unit days with SIRS. Secondary endpoints were the incidence of SIRS, SIRS criteria per day, duration of invasive mechanical ventilation, intensive care unit length of stay, the incidence of acute lung injury, maximum C-reactive protein, maximum white blood cell count, incidence of new candida and/or central-line-associated bloodstream infections, incidence of new thromboembolic complications, cumulative insulin requirements and presence of hyper- or hypoglycemia. RESULTS: The study groups did not differ in any baseline variable. There was no difference in the number of days in the intensive care unit with SIRS between microfilter and control patients [2 (0.8-4.7) vs. 1.8 (0.7-4.4), p = 0.62]. Except for a higher incidence of SIRS in microfilter patients (99.6 vs. 96.8 %, p = 0.04), no difference between the groups was observed in any secondary outcome parameter. Results did not change when only patients with an intensive care unit length of stay of greater than 7 days were included in the analysis. The rate of adverse events was comparable between microfilter and control patients. In two patients allocated to the microfilter group, the study intervention was discontinued for technical reasons. Use of in-line microfilters was associated with additional costs. CONCLUSIONS: The use of in-line microfilters failed to modulate systemic inflammation and clinical outcome parameters in critically ill adults. TRIAL REGISTRATION: Clinical Trials NCT01534390.

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.

Renal replacement therapy with regional citrate anticoagulation as an effective method to treat hypercalcemic crisis.

Hemodialysis is considered the renal replacement technique of choice to control life-threatening hypercalcemia. In this case series, the experience with continuous venovenous hemodiafiltration (CVVHDF) with regional citrate anticoagulation to control five hypercalcemic crises in four patients is summarized. Overall maximum ionized and total calcium levels ranged from 1.72 to 2.01 mmol/L and 3.1 to 4.2 mmol/L, respectively. All patients presented with impaired consciousness, cardiac arrhythmias, or acute oliguria, despite therapy. Trisodium citrate was administered at 3 mmol/h (hourly calcium replacement 1.15-2.75 mmol). This allowed a controlled decrease in ionized calcium levels below 1.4 mmol/L within 4 hours (interquartile range [IQR], 2.5-10) and resolution of neurological symptoms within 15.5 hours (IQR, 12-22.8). The duration of CVVHDF was 1 day in those patients in whom hypercalcemia was the reason for admission. Four asymptomatic episodes of mild hypocalcemia occurred in two patients. No patient developed relevant abnormalities of serum sodium levels or pH, experienced cardiac arrhythmia, or required transfusion of blood products during CVVHDF. One patient with metastatic bronchial carcinoma experienced rebound hypercalcemic crisis 13 days after a 1 day session of CVVHDF with regional citrate anticoagulation. In conclusion, CVVHDF with regional citrate anticoagulation appears to be effective and potentially safe to rapidly normalize calcium levels in hypercalcemic crisis.

The arterial blood pressure associated with terminal cardiovascular collapse in critically ill patients: a retrospective cohort study.

INTRODUCTION: Liberal and overaggressive use of vasopressors during the initial period of shock resuscitation may compromise organ perfusion and worsen outcome. When transiently applying the concept of permissive hypotension, it would be helpful to know at which arterial blood pressure terminal cardiovascular collapse occurs. METHODS: In this retrospective cohort study, we aimed to identify the arterial blood pressure associated with terminal cardiovascular collapse in 140 patients who died in the intensive care unit while being invasively monitored. Demographic data, co-morbid conditions and clinical data at admission and during the 24 hours before and at the time of terminal cardiovascular collapse were collected. The systolic, mean and diastolic arterial blood pressures immediately before terminal cardiovascular collapse were documented. Terminal cardiovascular collapse was defined as an abrupt (<5 minutes) and exponential decrease in heart rate (> 50% compared to preceding values) followed by cardiac arrest. RESULTS: The mean ± standard deviation (SD) values of the systolic, mean and diastolic arterial blood pressures associated with terminal cardiovascular collapse were 47 ± 12 mmHg, 35 ± 11 mmHg and 29 ± 9 mmHg, respectively. Patients with congestive heart failure (39 ± 13 mmHg versus 34 ± 10 mmHg; P = 0.04), left main stem stenosis (39 ± 11 mmHg versus 34 ± 11 mmHg; P = 0.03) or acute right heart failure (39 ± 13 mmHg versus 34 ± 10 mmHg; P = 0.03) had higher arterial blood pressures than patients without these risk factors. Patients with severe valvular aortic stenosis had the highest arterial blood pressures associated with terminal cardiovascular collapse (systolic, 60 ± 20 mmHg; mean, 46 ± 12 mmHg; diastolic, 36 ± 10 mmHg), but this difference was not significant. Patients with sepsis and patients exposed to sedatives or opioids during the terminal phase exhibited lower arterial blood pressures than patients without sepsis or administration of such drugs. CONCLUSIONS: The arterial blood pressure associated with terminal cardiovascular collapse in critically ill patients was very low and varied with individual co-morbid conditions (for example, congestive heart failure, left main stem stenosis, severe valvular aortic stenosis, acute right heart failure), drug exposure (for example, sedatives or opioids) and the type of acute illness (for example, sepsis).