Sequential Extracorporeal Blood Purification Is Associated with Prolonged Survival among ICU Patients with COVID-19 and Confirmed Bacterial Superinfection.

INTRODUCTION: This study investigates the impact of sequential extracorporeal treatments with oXiris® or CytoSorb® plus Seraph-100® on the clinical and laboratory parameters of critically ill COVID-19 patients with bacterial superinfection. METHODS: Patients admitted to the intensive care unit with COVID-19, bacterial superinfection, and undergoing blood purification (BP) were enrolled in this prospective, single-center, observational study. "standard BP" with oXiris® or CytoSorb® were used in 35 COVID-19 patients with bacterial infection. Seraph-100® was added in 33 patients when available serially in the same oXiris® circuit or as sequential treatment with CytoSorb® as a sequential BP. RESULTS: A significant reduction in SOFA score 3 days after treatment was observed in patients undergoing sequential BP (11.3 vs. 8.17, p < 0.01) compared to those undergoing "standard BP" (11.0 vs. 10.3, p > 0.05). The difference between the observed and expected mortality rate based on APACHE IV was greater in the sequential BP group (42.4% vs. 81.7%, p < 0.001) than the "standard BP" (74.2% vs. 81.7%, p > 0.05). Patients treated with sequential BP had a longer survival than those treated with "standard BP" (22.4 vs. 18.7 months; p < 0.001). CONCLUSIONS: The sequential approach may enhance the positive effect of BP on organ dysfunction among critically ill patients with COVID-19 and bacterial superinfection.

Safety and efficacy of fluvoxamine in COVID-19 ICU patients: An open label, prospective cohort trial with matched controls.

AIMS: Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) and sigma-1 receptor agonist, has so far shown promise in the prevention of COVID-19 progression as an early treatment option in three trials. The aim of this study was to evaluate the safety and efficacy of fluvoxamine in COVID-19 patients if administered later in the course of the disease. METHODS: The study was designed as an open-label, prospective cohort trial with matched controls. In April and May 2021, 51 ICU COVID-19 patients hospitalised in the University Hospital Dubrava and University Hospital Centre Zagreb, Croatia, were treated with fluvoxamine 100 mg three times daily for 15 days in addition to standard therapy and they were prospectively matched for age, gender, vaccination against COVID-19, disease severity and comorbidities with 51 ICU controls. RESULTS: No statistically significant differences between groups were observed regarding the number of days on ventilator support, duration of ICU or total hospital stay. However, overall mortality was lower in the fluvoxamine group, 58.8% (n = 30/51), than in the control group, 76.5% (n = 39/51), HR 0.58, 95% CI (0.36-0.94, P = .027). CONCLUSION: Fluvoxamine treatment in addition to the standard therapy in hospitalised ICU COVID-19 patients could have a positive impact on patient survival. Further studies on the effects of fluvoxamine in COVID-19 patients are urgently required.

ANESTHESIA FOR ROBOT-ASSISTED RADICAL PROSTATECTOMY - A CHALLENGE FOR ANAESTHESIOLOGIST.

Mininimally invasive surgery has become one of the most popular ones over the last few decades due to many benefits. The advantages are minimal surgical incision, reduced blood loss, reduced postoperative pain, faster postoperative recovery, shorter hospital stay, lower morbidity and better outcomes compared to open surgery. The most common robotic procedures in urology are radical prostatectomies. In UHC Zagreb, since November 2019 until now, there have been more than 180 robotic assisted radical prostatectomies (RALP) using Senhance robotic system performed. As a procedure with many possible complications, it represents a challenge for anaesthesiologist. Some of the problems the anaesthesiologists have to face are related to limited patient access, possible difficulties connected with positioning, pneumoperitoneum, subcutaneous emphysema, possible airway oedema. Pneumoperitoneum has impact on almost every system: cardiovascular, renal, respiratory, gastrointestinal and other. Detailed understanding of physiological changes of RALP, with intraoperative impact on nearly every body system is ultimate. Careful preoperative evaluation and intraoperative conduction minimize the risk of complications, and help patients to reach full recovery in a very short time. Excellent outcomes are the result of individualized approach to the patient and good communication between team members.

Caesarean Section and the Risk of Postpartal Depression: Is There a Possible Role of Heat Shock Proteins?

Data on the potential connection between surgical stress during caesarean section and the role of heat shock proteins in development of postpartal depression is lacking in the literature. This is a narrative review with a goal to establish the potential role of heat shock proteins during caesarean section and development of postpartal depression. Systemic hyperinflammatory state, such as the one that occurs during surgery, may trigger protective cell reaction, which is usually called the heat shock response. Results of several researches bring strong evidence of correlation between expression of genes coding for family of heat shock proteins with the onset of depressive symptoms. Also, a recent meta-analysis established caesarean section as a risk factor for development of postpartal depression. It is obvious that heat shock proteins play a certain role in development of psychiatric disorders. However, a role of heat shock proteins in development of postpartal depression remains open for debate. We emphasise the need for a randomised control trial which would enable an answer to the mentioned issue.

Prevalence of Gestational Diabetes Mellitus and Perinatal Outcomes According to the Old Who Criteria and IADPSG Criteria.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy. Pregnancies with GDM have worse outcomes compared to pregnancies with normal glucose tolerance. The objectives of the study were to determine the prevalence of GDM and perinatal outcomes according to the old WHO criteria and IADPSG criteria. SUBJECTS AND METHODS: A retrospective study included 2,405 pregnant women who delivered between January 2009 and December 2010. According to the OGTT results, pregnant women were divided into 4 groups. We analyzed the prevalence of GDM, characteristics of pregnant women and their newborns and perinatal outcomes. RESULTS: We found significantly higher prevalence of GDM according to the IADPSG criteria compared to the WHO criteria. Pregnant women with GDM were significantly older, had higher pre-pregnancy BMI, fasting and 2-h plasma glucose. Pregnant women with GDM had worse pregnancy outcomes compared to control group. The overall proportion of overweight and obese pregnant women was the highest in the group of untreated pregnant women with GDM according to the IADPSG criteria. In this group we found significantly higher rate of fetal macrosomia and LGA. The rate of caesarean section was significantly higher in comparison to control group. Pre-eclampsia was significantly more common in groups of pregnant women with GDM compared to control group. CONCLUSION: IADPSG diagnostic criteria reveals more women with hyperglycemic disorders in pregnancy. A group of pregnant women who were normoglycemic according to the WHO criteria, but according to the IADPSG were diagnosed GDM, had adverse pregnancy outcomes. Lower values of glycemia, than those defined for diabetes in pregnancy, are associated with adverse pregnancy outcomes.

Oral Cavity Colonization with Multidrug-Resistant Gram-Negative Bacteria after Preoperative Prophylactic Use of Antibiotics as a Risk Factor for Ventilator-Associated Pneumonia.

BACKGROUND: Although it was previously shown that prolonged prophylactic antibiotic exposure and multiple inadequate antibiotic therapies are independent risk factors for multidrug-resistant ventilator associated pneumonia there were no studies investigating whether pre-operative prophylactic dose of antibiotics changes oral microbiome and increases the risk of ventilator associated pneumonia. The aim of the study was to determine if pre-operative prophylactic dose of antibiotics affects the oral microbiome, increases the colonization with Gram-negative bacteria and subsequent risk of ventilator associated pneumonia. SUBJECTS AND METHODS: Mechanically ventilated adult patients receiving surgical antibiotic prophylaxis were included in the study. The presence of Gram negative microorganisms in the pre-prophylactic and post-prophylactic oral swabs and tracheal aspirates, as well as the occurrence of ventilator associated pneumonia, were analyzed. RESULTS: Number of patients colonized with Gram negative bacteria in post- prophylactic oral swab was significantly higher compared to oral swab taken before prophylactic antibiotic. On the other hand, the number of patients with Gram- negative bacteria in tracheal aspirates remained similar as in post- prophylactic oral swabs. Moreover, we found that presence of Gram- negative bacteria in both pre- and post- prophylactic oral swabs was in the positive correlation with the presence of Gram- negative bacteria in tracheal aspirates. CONCLUSIONS: This study showed increased colonization of oral cavity with Gram- negative bacteria after preoperative prophylactic antibiotics. Furthermore, receiving two prophylactic antibiotics from WHO Watch list increased the incidence of Gram- negative bacteria in oral swabs and tracheal aspirates, and the risk of ventilator associated pneumonia development.

Therapeutic Mechanisms of Ketamine.

Major depressive disorder is the greatest burden of developed countries in the context of morbidity caused by mental disorders. Until recent, ketamine has been mostly used for anesthesia, analgesia, sedation and treatment of chronic pain syndromes. However, unique pharmacodynamic properties of ketamine have increased interests in it's use for treatment of depression. It is assumed that ketamine reverses synaptic chronic stress pathology within one day of administration by postsynaptic glutamate activation, providing synaptic connectivity restoration that last for days or weeks. Potential glutamatergic agents, in context of treatment of major depressive disorder are not entirely novel phenomenon. Considering the aforementioned, current neurobiological view of depression as a solely monoaminergic phenomenon should be reassessed in order to prompt discovery of putative antidepressant drugs of novel generation. Acute side effects, such as increased salivation, increase in heart rate, systemic arterial pressure and intracranial pressure necessitate careful monitoring during intravenous administration of ketamine, even in subanesthetic doses. However, major burden of ketamine administration lies in it's ability to produce psychotomimetic side effects and emergence delirium. Esketamine nasal spray has now been widely approved and is considered safe in terms of acute side effects, tolerability and consistent therapeutic benefit.

Allergic reactions to colloid fluids in anesthesia.

Allergic reactions in anesthesia are a rare event, however, might be life threatening when occurred. Clinical manifestations may not be indicative at first, and difficult to differentiate from different situations during operation and anesthesia. Colloids represent a group of fluids often used during perioperative period that, among other adverse reactions, have an allergic potential. Albumin is a natural colloid that has the lowest incidence of these reactions. However, it is found as an additional substance in other blood products, and, therefore, has to be taken into consideration if anaphylaxis occurs. Dextrans cause the most severe reactions due to dextran reactive antibodies. Pretreatment with Dextran 1 may inhibit the reaction. Gelatins have the highest incidence of anaphylaxis among colloids. Patients with history of allergy to some food, vaccines, cosmetics containing gelatin are at greater perioperative risk for anaphylaxis. Not to forget, gelatins are also a part of topical haemostatic agents used in surgery. Testing for colloid allergies is limited due to their pathophysiologic mechanism, so the clinical assessment is usually essential. Treatment of anaphylaxis caused by colloids is the same as for any other cause. This is a review of the most common colloids and their association with allergic reactions in everyday practice.

Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials.

Photoplethysmographic evaluation of sympathectomy during lumbar epidural analgesia: A randomized comparison of 0.125% ropivacaine and 0.125% levobupivacaine.

BACKGROUND: There are no data on the difference between the impact of ropivacaine and levobupivacaine on sympathetic nerve fibers during central neuraxial blocks. We hypothesized that there is no difference in the degree of sympathectomy between the two drugs during lumbar epidural analgesia for labor pain. METHODS: Sixty healthy parturients were randomized to the type of local anesthetic-opiod solution administered in the epidural space: 10 mL of 0.125% ropivacaine + 100 mcg of fentanyl or 10 mL of 0.125% levobupivacaine + 100 mcg of fentanyl. After the baseline measurement, photoplethysmography signal from the first toe of the leg was recorded 5, 10 and 20 minutes after administration of epidural analgesia. RESULTS: Area under the curve and the pulse transit time of the toe photoplethysmography increased in both groups during the first 20 minutes after administration of epidural analgesia (P < 0.001 for both parameters in both groups). No difference in the degree of sympathectomy was found between the groups for the area under the curve. The difference in the change of the pulse transit time suggests that the two local anesthetics might differ in the degree of sympathectomy (P = 0.024). CONCLUSION: 0.125% ropivacaine and 0.125% levobupivacaine do not differ in the terms of sympathectomy-mediated side effects of the epidural block for labor analgesia. However, the photoplethysmography findings suggest a certain difference in the degree of sympathectomy between the two local anesthetics.

Anaphylaxis during pregnancy.

Anaphylaxis occuring during pregnancy has a potential to cause devastating damage to the unborn baby and the mother. However, majority of adverse outcomes of anaphylaxis during pregnancy frequently affect the neonates rather than the mothers. The negative neurologic outcomes of the fetus are mostly due to delayed caesarean delivery or inadequate doses of adrenaline during anaphylaxis. Most of the current knowledge on this clinical scenario is based on case reports and very few review articles. This is a mini review of the causes, diagnosis and management of anaphylaxis occuring during pregnancy.

FALSE POSITIVE PHENOTYPIC DETECTION OF METALLO-BETA-LACTAMASES IN ACINETOBACTER BAUMANNII.

Phenotypic detection of metallo-ß-lactamases (MBLs) in Acinetobacter (A.) baumannii is a serious challenge to clinical microbiologists. MBLs are inhibited by metal chelators such as ethylenediaminetetraacetic acid) (EDTA). Production of MBLs cannot be recognized based on resistance phenotype. Therefore, phenotypic tests using EDTA are recommended. The aim of this study was to investigate the sensitivity and specificity of inhibitor based tests (EDTA) for detection of MBL. A total of 172 A. baumannii strains (123 carbapenemase positive and 49 carbapenemase negative) were analyzed. Phenotypic detection of MBLs was performed by the combined disk test with EDTA (CDT-EDTA) and EPI-dilution test (EPI-DT). Both tests were positive in all 11 isolates possessing VIM-1 MBL, showing 100% sensitivity. However, false positive results were observed in strains with class D carbapenemases using both tests, i.e. all OXA-23 and OXA-24/40 producing organisms and most OXA-58 positive strains (77% with CDT-EDTA vs. 65% with EPI-DT). False positive results can occur because oxacillinases are converted to a less active state in the presence of EDTA, leading to augmentation of the inhibition zone around the carbapenem disk or reduction of carbapenem minimum inhibitory concentrations. This study showed high sensitivity but low specificity of phenotypic methods in the detection of MBLs.

Allergic reactions and anesthesia.

The diagnosis of allergic reactions during anesthesia is difficult. For example, cardio-respiratory symptoms may be due to the accompanying pharmacological effects of anesthetics and poor interpretation of the reaction during anesthesia. It is important to distinguish whether a real allergic reaction has occurred. Accidents with anesthetics and muscle relaxants are observed more often than we expect. Proper anaphylaxis rarely occurs during anesthesia (1: 20000). Muscle relaxants are the most common causes, followed by latex, chlorhexidine, antibiotics and opioids. To confirm the diagnosis it is necessary to perform a larger number of blood and skin tests. Targeted diagnostic approach and therapy allow avoiding more difficult events. Anesthesia should be selected for those medications that have been tested. Additionally, patients should be premedicated with antihistaminics and systemic steroids, as the emergence of intolerance is not completely excluded by negative testing. There is no gold standard for testing, even if every method is precisely performed; there are always false positive and false negative results. When anaphylaxis appears, urgent approach is needed to provide the patient with appropriate treatment. It is necessary to act according to the established algorithms and treatment protocols. Many anesthesiologists will not ever see such a reaction, and very few will see more than one during their work life. Awareness of allergy in anesthesia is still insufficient.

Acute Coronary Syndrome with ST-segment Elevation in Pregnancy: Anesthetic Management of Delivery.

Acute coronary syndrome (ACS) during pregnancy is rare but may be associated with high risk complications. Approximately 150 myocardial infarctions (MI) during pregnancy have been documented in literature worldwide, but we didn't find one with myocardial aneurysm. We describe 2 patients with acute MI; both with ST segment elevation (STEMI), 1 case complicated with heart failure, formation of a myocardial aneurysm and broad QRS arrhythmia; another with uncomplicated course, and their anesthetic management during delivery. Acute MI is rare in reproductive age usually developing in women with cardiovascular risk factors. There is concern about its rising incidence due to the increase of average maternal age. Our cases show that there might be some undiscovered risk factors for pregnancy related myocardial infarction.

Efficacy and Safety of High PEEP NIV in COVID-19 Patients.

OBJECTIVE: To investigate the efficacy and safety of non-invasive ventilation (NIV) with high PEEP levels application in patients with COVID-19-related acute respiratory distress syndrome (ARDS). METHODS: This is a retrospective cohort study with data collected from 95 patients who were administered NIV as part of their treatment in the COVID-19 intensive care unit (ICU) at University Hospital Centre Zagreb between October 2021 and February 2022. The definite outcome was NIV failure. RESULTS: High PEEP NIV was applied in all 95 patients; 54 (56.84%) patients could be kept solely on NIV, while 41 (43.16%) patients required intubation. ICU mortality of patients solely on NIV was 3.70%, while total ICU mortality was 35.79%. The most significant difference in the dynamic of respiratory parameters between 2 patient groups was visible on Day 3 of ICU stay: By that day, patients kept solely on NIV required significantly lower PEEP levels and had better improvement in PaO2, P/F ratio, and HACOR score. CONCLUSION: High PEEP applied by NIV was a safe option for the initial respiratory treatment of all patients, despite the severity of ARDS. For some patients, it was also shown to be the only necessary form of oxygen supplementation.

Successful delivery of fetus with fetal inherited thrombophilia after two fetal deaths.

A pregnant woman with inherited thrombophilia (factor II mutation--20210A) had two late pregnancy losses. The first pregnancy was not well documented, but the second pregnancy was complicated by fetal thrombophilia and umbilical artery thrombosis, proven after fetal death. During the third pregnancy enoxaparine was introduced in the therapy and early amniocentesis was performed. Fetal thrombophilia was proven again. Early delivery was induced and performed with no complications, resulting in a live healthy infant. A history of miscarriages or recurrent fetal loss should raise suspicion of thrombophilia as a potential cause. It is debatable whether amniocentesis in pursuit of fetal thrombophilia should be performed and whether this will lead to a better perinatal outcome. When fetal thrombophilia is diagnosed, an earlier induction of delivery should be considered, taking into account the fetal extrauterine viability. The aforementioned approach of early delivery in cases of inherited fetal thrombophilia could be a possible solution for better perinatal outcomes.

Intermittent epidural TOP-UPS vs. patient control epidural analgesia during labor.

Pain during labor and delivery is often very unpleasant and stressful for the parturients. Patient controlled epidural analgesia (PCEA) has been found to be both safe and effective, providing optimal pain relief and allowing women to participate in their own analgesia). Compared to other epidural techniques, intermittent epidural top-ups and continuous epidural analgesia (CEA), PCEA uses diluted local anesthetic solutions with less motor block and less unscheduled clinician interventions. The purpose of our study was to compare intermittent bolus epidural top-ups and PCEA in labor. Sixty ASA I patients who requested epidural analgesia for labor and had written consent were included in the study. 30 patients in the first group received intermittent bolus epidural top-ups, while patients in the second group received PCEA. We evaluated duration of labor, maternal sense of pain using VAS scale and maternal satisfaction during fetal descent in both groups. We found that the duration of labor was significantly shorter and maternal sense of pain was lower in the PCEA group than in the group receiving epidural bolus top-ups. There were no differences between groups in maternal satisfaction during fetal descent.

Interleukin-6 polymorphism and prostate cancer risk in population of Eastern Croatia.

Recent studies suggest that chronic inflammation is crucial in the development and progression of prostate cancer (CaP). Interleukin-6 (IL-6) is a proinflammatory cytokine that plays an important role in intraprostatic inflammation and thus carcinogenesis. The -174G > C polymorphism of IL-6 gene has been associated with high IL-6 producer phenotype and an increased risk for CaP. The aim of this study was to evaluate the association between the mentioned IL-6 polymorphism and CaP risk, as well as to compare the genotype frequency between the different tumour grades of CaP, in population of Eastern Croatia. We analyzed the IL-6 polymorphism in 120 CaP patients and 120 controls with benign prostatic hyperplasia (BPH). CaP patients and BPH controls did not statistically differ in studied IL-6 polymorphism. Furthermore, high IL-6 producer genotypes (GG or GC) were more frequent in controls than in CaP group (86.7% vs 80.8%, respectively, p = 0.147). Also, no statistically significant difference in IL-6 high and low producer genotype frequency was noticed between well, moderately and poorly differentiated tumours. Our results, taken together with other studies on the subject, suggest that IL-6 - 174 single nucleotide polymorphism (SNP) distribution may differ between various ethnic groups and that a single cytokine gene polymorphism has probably just a minor effect on CaP susceptibility. Further studies should be performed to clarify the link between SNPs of different cytokines and the risk for CaP.

Multidrug-Resistant Bacteria in a COVID-19 Hospital in Zagreb.

During November to December 2020, a high rate of COVID-19-associated pneumonia with bacterial superinfections due to multidrug-resistant (MDR) pathogens was recorded in a COVID-19 hospital in Zagreb. This study analyzed the causative agents of bacterial superinfections among patients with serious forms of COVID-19. In total, 118 patients were hospitalized in the intensive care unit (ICU) of the COVID-19 hospital. Forty-six out of 118 patients (39%) developed serious bacterial infection (VAP or BSI or both) during their stay in ICU. The total mortality rate was 83/118 (70%). The mortality rate due to bacterial infection or a combination of ARDS with bacterial superinfection was 33% (40/118). Six patients had MDR organisms and 34 had XDR (extensively drug-resistant). The dominant species was Acinetobacter baumannii with all isolates (34) being carbapenem-resistant (CRAB) and positive for carbapenem-hydrolyzing oxacillinases (CHDL). One Escherichia coli causing pneumonia harboured the blaCTX-M-15 gene. It appears that the dominant resistance determinants of causative agents depend on the local epidemiology in the particular COVID center. Acinetobacter baumannii seems to easily spread in overcrowded ICUs. Croatia belongs to the 15 countries in the world with the highest mortality rate among COVID-19 patients, which could be in part attributable to the high prevalence of bacterial infections in local ICUs.

Individualized Management of Coagulopathy in Patients with End-Stage Liver Disease.

Over the last decades, individualized approaches and a better understanding of coagulopathy complexity in end-stage liver disease (ESLD) patients has evolved. The risk of both thrombosis and bleeding during minimally invasive interventions or surgery is associated with a worse outcome in this patient population. Despite deranged quantitative and qualitative coagulation laboratory parameters, prophylactic coagulation management is unnecessary for patients who do not bleed. Transfusion of red blood cells (RBCs) and blood products carries independent risks for morbidity and mortality, including modulation of the immune system with increased risk for nosocomial infections. Optimal coagulation management in these complex patients should be based on the analysis of standard coagulation tests (SCTs) and viscoelastic tests (VETs). VETs represent an individualized approach to patients and can provide information about coagulation dynamics in a concise period of time. This narrative review will deliver the pathophysiology of deranged hemostasis in ESLD, explore the difficulties of evaluating the coagulopathies in liver disease patients, and examine the use of VET assays and management of coagulopathy using coagulation factors. Methods: A selective literature search with PubMed as the central database was performed with the following.