Coronavirus disease 2019 (COVID-19): update for anesthesiologists and intensivists March 2020.

The current outbreak of coronavirus disease (COVID-19) has reached Germany. The majority of people infected present with mild disease, but there are severe cases that need intensive care. Unlike other acute infectious diseases progressing to sepsis, the severe courses of COVID19 seemingly show prolonged progression from onset of first symptoms to life-threatening deterioration of (primarily) lung function. Diagnosis relies on PCR using specimens from the respiratory tract. Severe ARDS reflects the hallmark of a critical course of the disease. Preventing nosocomial infections (primarily by correct use of personal protective equipment) and maintenance of hospitals' operational capability are of utmost importance. Departments of Anaesthesia, Intensive Care and emergency medicine will envisage major challenges.

[Coronavirus disease 2019 (COVID-19): update for anesthesiologists and intensivists March 2020]. / "Coronavirus disease 2019" (COVID-19): update für Anästhesisten und Intensivmediziner März 2020.

The current outbreak of coronavirus disease (COVID-19) has reached Germany. The majority of people infected present with mild disease, but there are severe cases that need intensive care. Unlike other acute infectious diseases progressing to sepsis, the severe courses of COVID19 seemingly show prolonged progression from onset of first symptoms to life-threatening deterioration of (primarily) lung function. Diagnosis relies on PCR using specimens from the respiratory tract. Severe ARDS reflects the hallmark of a critical course of the disease. Preventing nosocomial infections (primarily by correct use of personal protective equipment) and maintenance of hospitals' operational capability are of utmost importance. Departments of Anaesthesia, Intensive Care and emergency medicine will envisage major challenges.

Intraoperative reduction of vasopressors using processed electroencephalographic monitoring in patients undergoing elective cardiac surgery: a randomized clinical trial.

Intraoperative vasopressor and fluid application are common strategies against hypotension. Use of processed electroencephalographic monitoring (pEEG) may reduce vasopressor application, a known risk factor for organ dysfunction, in elective cardiac surgery patients. Randomized single-centre clinical trial at Jena University Hospital. Adult patients operated on cardiopulmonary bypass or off-pump coronary artery bypass grafting were randomised to receive anesthesia with visible or blinded pEEG using Narcotrend™. In blinded-Narcotrend (NT) depth of anesthesia was extrapolated from clinical signs, hemodynamic response and anesthetic concentration, supplemented by target indices between 37 and 64 in the visible-NT group. Intraoperative norepinephrine requirement (primary endpoint), fluid balance, extubation time, delirium occurrence and adverse events were evaluated. Patients of the intent-to-treat population (visible-NT: n = 123, blinded-NT: n = 122) had similar patient and procedural characteristics. Adjusted for type of surgery intraoperative Norepinephrine application was significantly reduced in visible-NT (n = 120, robust mean of cumulative dose 4.71 µg/kg bodyweight) compared to blinded-NT patients (n = 119, 6.14 µg/kg bodyweight) (adjusted robust mean difference 1.71 (95% CI 0.33-3.10) µg/kg bodyweight). Although reduction in patients operated on cardiopulmonary bypass was higher the interaction was not significant in post-hoc subgroup analysis. Intraoperative fluid balance was similar among both groups and strata. Extubation time was non-significantly lower in visible than in blinded-NT group. Overall postoperative delirium risk was 16.4% without differences among the groups. Adverse events-sudden movement/coughing, perspiration or hypertension-occurred more often with visible-NT, while one blinded-NT patient experienced intraoperative awareness. Titration of depth of anesthesia in elective cardiac surgery patients using pEEG allows to reduce application of norepinephrine.

Fast simultaneous assessment of renal and liver function using polymethine dyes in animal models of chronic and acute organ injury.

Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.

Impact of perioperative liver dysfunction on in-hospital mortality and long-term survival in infective endocarditis patients.

PURPOSE: Infective endocarditis (IE) is often associated with multiorgan dysfunction and mortality. The impact of perioperative liver dysfunction (LD) on outcome remains unclear and little is known about factors leading to postoperative LD. METHODS: We performed a retrospective, single-center analysis on 285 patients with left-sided IE without pre-existing chronic liver disease referred to our center between 2007 and 2013 for valve surgery. Sequential organ failure assessment (SOFA) score was used to evaluate organ dysfunction. Chi-square, Cox regression, and multivariate analyses were used for evaluation. RESULTS: Preoperative LD (Bilirubin >20 µmol/L) was present in 68 of 285 patients. New, postoperative LD occurred in 54 patients. Hypoxic hepatitis presented the most common origin of LD, accompanied with high short-term mortality. In-hospital mortality was higher in patients with preoperative and postoperative LD compared to patients without LD (51.5, 24.1, and 10.4%, respectively, p < 0.001). 5-year survival was worse in patients with pre- or postoperative LD compared to patients without LD (20.1, 37.1, and 57.0% respectively). A landmark analysis revealed similar 5-year survival between groups after patient discharge. Quality of life was similar between groups when patients survived the perioperative period. Logistic regression analysis identified duration of cardiopulmonary bypass and S. aureus infection as independent predictors of postoperative LD. CONCLUSIONS: Perioperative liver dysfunction in patients with infective endocarditis is an independent predictor of short- and long-term mortalities. After surviving the hospital stay, 5-year prognosis is not different and quality of life is not affected by LD. S. aureus and duration of cardiopulmonary bypass represent risk factors for postoperative LD.

[Monitoring of liver function in the critically ill]. / Monitoring der Leberfunktion bei Intensivpatienten.

Liver failure and hepatic dysfunction represent diagnostic and therapeutic challenges for the intensivist. Besides acute liver failure, hypoxic hepatitis, sepsis and (secondary) sclerosing cholangitis may lead to massive liver dysfunction with subsequent multiorgan dysfunction syndrome that limits survival. Among classical laboratory parameters (so-called static liver parameters) liver function tests may help with the diagnosis to allow early treatment or prevention of liver dysfunction. The aim of this article is to present the current aspects of liver function monitoring and to provide guidelines to the intensivist for diagnosing liver dysfunction in the intensive care setting.

[Current aspects of diagnostics of hepatic dysfunction in critically ill]. / Aktuelle Aspekte zur Diagnostik der hepatischen Dysfunktion beim kritisch Kranken.

Hepatic dysfunction may develop in critically ill patients in the course of extrahepatic diseases such as sepsis and is frequently limiting prognosis. Conventional "static" laboratory parameters assess hepatocellular damage, synthetic function or cholestasis, providing informations about (differential) diagnostic aspects, while their significance to assess rapid changes in flow and function in the critical care setting is limited. In contrast, quantitative (or "dynamic") liver function tests, such as measurement of plasma disappearance rate of indocyanine green (PDRICG) or 13C-methacetin metabolism, assess specific metabolic and/or excretory function of the liver together with sinusoidal perfusion at the time of measurement and can detect liver dysfunction early in the course of critical illness. In addition, PDRICG demonstrated prognostic significance, albeit, severity of canalicular excretory dysfunction might be underestimated. For chronic liver disease, scoring systems, such as the Child-Turcotte-Pugh-score or the MELD, were developed to assess severity of disease and probability of survival. Scoring systems are also used for graft allocation. Combining scoring systems with dynamic tests holds the potential to improve predictive value, e.g. in the transplant setting.

[Monitoring of plasma disappearance rate of indocyanine green in a patient with necrotizing fasciitis and septic shock]. / Uberwachung der Plasmaeliminationsrate von Indocyaningrün bei einem Patienten mit nekrotisierender Fasziitis und septischem Schock.

HISTORY AND ADMISSION FINDINGS: A 45-year old man with diabetes mellitus and arterial hypertension was transferred with fever of unknown origin, suspected diabetic angiopathy and sepsis. On admission the patient presented all signs of septic shock. Livid coloured injuries on his right hand and petechial bleeding in distal extremities were observed. INVESTIGATIONS: A different origin of sepsis was not found in transesophageal ultrasound cardiography and computed tomography of cranium, chest and abdomen. DIAGNOSIS, TREATMENT AND COURSE: Immediately after admission early goal-directed therapy was initiated. Apart from calculated antibiotic therapy intensive insulin therapy and hydrocortisone substitution was begun. The patient presented a multiple organ dysfunction syndrome. Plasma disappearance rate of indocyanine green (PDR (ICG)) on admission was 20,4 %/min (normal range > 18 %/min) and fell to 6,8 %/min within 12 hours, while central venous oxygen saturation remained normal. Despite therapy according to current guidelines for severe sepsis, the patient deteriorated. Surgical debridement was performed suspecting necrotizing fasciitis and application of recombinant human activated protein C (rhAPC) started. PDR (ICG) rapidly raised to normal values; the patient recovered and was discharged after 9 days. CONCLUSIONS: Monitoring of PDR (ICG) allows for improved bedside evaluation of liver perfusion of the critically ill and is not only able to predict prognosis but may help in decision making for supportive therapies.

[Acute liver failure. Current aspects of diagnosis and therapy]. / Akutes Leberversagen. Aktuelle Aspekte zur Diagnostik und Therapie.

Disturbances of some partial liver functions, such as synthesis, excretion, or biotransformation of xenobiotics, are important for prognosis and ultimate survival in patients presenting with multiple organ dysfunction on the intesive care unit (ICU). The incidence of liver dysfunction is underestimated when traditional "static" measures such as serum-transaminases or bilirubin as opposed to "dynamic" tests, such as clearance tests, are used to diagnose liver dysfunction. Similar to the central role of the failing liver in MODS, extrahepatic complications, such as hepatorenal syndrome and brain edema develop in acute or fulminant hepatic failure and determine the prognosis of the patient. This is reflected in the required presence of hepatic encephalopathy in addition to hyperbilirubinemia and coagulopathy for the diagnosis of acute liver failure. In addition to these clinical signs, dynamic tests, such as indocyanine green clearance, which is available at the bed-side, are useful for the monitoring of perfusion and global liver function. In addition to specific and causal therapeutic interventions, e.g. N-acetylcysteine for paracetamol poisoning or termination of pregnancy for the HELLP-syndrome, new therapeutic measures, e.g. terlipressin/albumin or albumin dialysis are likely to improve the poor prognosis of acute-on-chronic liver failure. Nevertheless, liver transplantation remains the treatment of choice for fulminant hepatic failure when the expected survival is <20%.

[Methemoglobinemia due to prilocaine after plexus anesthesia. Reduction by prophylactic administration of ascorbic acid?]. / Methämoglobinämie durch Prilocain nach Plexusanästhesien. Reduktion durch prophylaktische Gabe von Ascorbinsäure?

OBJECTIVE: This study investigated in vivo and in vitro kinetics of o-toluidine-induced methemoglobinemia and the influence of ascorbic acid on resulting methemoglobin concentrations. o-Toluidine is a metabolite of prilocaline and ascorbic acid is recommended for treatment of methemoglobinemia as an alternative to methylene blue. METHODS: We measured the formation of methemoglobin in vitro in a whole blood culture system of 8 healthy individuals 30, 60, and 360 min after the addition of different concentrations of o-toluidine (0.5, 5, 50 micrograms/ml) with and without addition of ascorbic acid (0.5 and 5 mg/ml). In a prospective randomized clinical study, a total of 72 patients of ASA risk I-III were investigated. The 3 groups of 24 patients received either an axillary, an infraclavicular vertical brachial plexus, or a combined femoral and ischiadic blockade. In each plexus anesthesia group, 12 patients were given 2,000 mg ascorbic acid intravenously before applying the local anesthetics. For surgery of the upper limb the patients received 40 ml 1% prilocaine and 10 ml 0.5% bupivacaine, for surgery of the lower limb they received 60 ml 1% prilocaine and 0.25 mg adrenaline. Blood samples for measurement of methemoglobin concentrations were taken before and 30, 60, 120, 180 and 360 min after the injection of the regional anesthetic. A p < 0.05 was considered to be significant. RESULTS: There was a dose-dependent increase of methemoglobin due to addition of o-toluidine after 360 min in vitro. The application of 0.5 mg/ml ascorbic acid to the whole blood samples with 0.5 and 5 micrograms/ml o-toluidine resulted in a further increase of methemoglobin formation whereas there was no difference in the samples with 50 micrograms/ml. The higher concentration of 5 mg/ml ascorbic acid attenuated the methemoglobin formation only with 50 micrograms/ml o-toluidine. No effect was observed with lower concentrations of o-toluidine. In the in vivo study plexus anesthesia with prilocaine resulted in an increase of the methemoglobin concentration with a maximum after 120-180 min. The highest measured methemoglobin concentration found was 11.3%. The methemoglobin concentration already showed a decrease 360 min after the application of the regional anesthetic 2,000 mg ascorbic acid given intravenously before plexus anesthesia was not able to influence the resulting methemoglobin concentrations. CONCLUSIONS: In vitro high concentrations of ascorbic acid are able to reduce the resulting methemoglobin concentration 360 min after addition of 50 micrograms/ml o-toluidine. The application of 2,000 mg ascorbic acid i.v. before plexus anesthesia with prilocaine does not reduce the concentration of methemoglobin.

[Using epidural anesthesia in patients with acute pancreatitis--prospective study of 121 patients]. / Anwendung der Epiduralanästhesie bei Patienten mit akuter Pankreatitis--Prospektive Untersuchung an 121 Patienten.

According to a previous study, an excellent level of analgesia can be expected when using epidural anaesthesia in patients with acute pancreatitis. In the present investigation, the effectiveness and safety of epidural anaesthesia is demonstrated in a large group of patients with severe acute pancreatitis, who were admitted to an intensive care unit. Epidural anaesthesia alone produced excellent analgesia on 1,083 of 1,496 observation days (72%) without the systemic use of other analgesic substances. Even in patients with marginal cardiovascular stability, epidural injection of local anaesthetic solution was tolerated well. Only 8% of all local anaesthetic injections were associated with a haemodynamic reaction that required pharmacological intervention. There was no case of a septic or neurological complication of epidural anaesthesia. Initially elevated serum amylase and lipase were normalized after 17.4 days (minimum one day, maximum 19 days). Surgical intervention was necessary for 36 patients, with a total of 64 surgeries having to be performed, including cholecystectomy. Sixteen patients required artificial ventilation for an average time of 12.3 days (minimum two days, maximum 48 days). Lethality was 2.5% (three patients), with all three patients suffering from an acute stage III pancreatitis. The average duration of ICU treatment was 12.4 days (minimum two days, maximum 101 days).