Search

Introduction. Coronavirus disease 2019 (COVID-19) is associated with high inflammatory response, hemostatic disturbances, and high thrombotic risk. Despite thromboprophylaxis, a high incidence of thromboembolic events has been reported with a consequent increase in anticoagulant therapy from standard to intermediate or even therapeutic doses. However, published evidence on the incidence and outcome of the hemorrhagic complications of applied therapy is still limited. Outlines of cases. We present two female COVID-19 patients, treated with anticoagulant therapy who suffered from major spontaneous bleeding and retroperitoneal hematoma. The first, a 64-year-old patient, treated with non-invasive ventilation protocol in the Intensive Care Unit due to respiratory failure received a therapeutic dose of anticoagulant therapy adjusted to the anti-Xa assay. The cumulative dose of nadroparin was 150 IU/kg body weight/day. The second, a 60-year-old patient with the moderate clinical presentation on low flow oxygen support was treated with therapeutic doses of anticoagulant therapy calculated according to the body weight. Emergency open surgery was performed due to massive bleeding. No active surgical bleeding was detected, and retroperitoneal hematomas were assumed to be complications of the applied anticoagulant therapy. Both patients were discharged and fully recovered. Conclusion. Although rare, severe hemorrhage requires attention when considering anticoagulant therapy in COVID-19. Uncommon sites of spontaneous bleeding suggest additional evaluation on a case-by-case basis, given that a diagnosis is often delayed due to a lack of specific presenting symptoms. Further studies are needed to verify the risk-benefit ratio of different regiments of anticoagulant therapy in patients with COVID-19.

Background/Aim. Sepsis represents a significant global burden, with an estimated 48.9 million cases and 11.0 million sepsis-related deaths recently recorded worldwide. The aim of this observational study was to assess a prognostic value of some readily available routine biomarkers: presepsin, procalcitonin, C-reactive protein (CRP), white blood cell (WBC) count, platelet count, mean platelet volume (MPV), and lactate, as well as their combination regarding the outcome in a cohort of critically ill adult patients with secondary sepsis. Methods. A total of 86 critically ill patients with secondary sepsis due to peritonitis, pancreatitis, and severe trauma, admitted to the surgical intensive care unit, were enrolled in this prospective study. Blood samples for biomarker analysis were collected in three time points: on admission (the 1st day) and on the 3rd, and 5th day after admission. The Sequential Organ Failure Assessment (SOFA) score, the Simplified Acute Physiology Score (SAPS) II, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score were calculated and recorded within the first 24 hours after admission (1st day). SOFA and SAPS II scores were recorded daily. The primary end-point was hospital mortality. Results. Values of each applied score were expectedly significantly higher in non-survivors in all time points. Regarding investigated parameters, only presepsin levels were significantly higher in non-survivors in all time points; MPV levels on the 3rd and 5th day; serum lactate levels on the 3rd day; CRP levels and WBC count on the 5th day. Clinical accuracy of parameters in predicting lethal outcomes was investigated in all time points. On the 1st day, apart from all three scores, only presepsin demonstrated statistically significant discriminative power regarding outcome (AUC of 0.670). Apart from SAPS II and SOFA score, on the 3rd day presepsin, MPV, and lactate (AUCs of 0.716, 0.667, and 0.642, respectively) and on the 5th day presepsin, MPV, CRP, and WBC count (AUCs of 0.790, 0.681, 0.643 and 0.654, respectively) were good predictors of the lethal outcome. Composite bioscore (presepsin, MVP, and lactate) on the 3rd day had the highest AUC of 0.820 in comparison with individual scores and parameters. The independent predictor of the lethal outcome on the 1st day was presepsin (p < 0.05) and on the 3rd day MPV (p < 0.01). Conclusion. Composite bioscore is superior to routine biomarkers and established scoring systems in predicting mortality in adult critically ill patients with secondary sepsis.

In December 2019, a new Corona virus (SARS-CoV-2) was identified as responsible for outbreak of viral pneumonia in Wuhan, Hubei Province, China. The World Health Organization has announced a pandemic of COVID-19 (Coronavirus disease 2019) on March 2nd 2020. COVID-19 is a respiratory infection where majority of patients have mild clinical symptoms. About 14% of patients require hospitalization and oxygen therapy and 5% of patients require admission to the intensive care unit. The most severe clinical cases include ARDS, sepsis and septic shock, acute renal failure, multiorgan dysfunction, and myocardial damage. Spread of the infection so far indicates that the number of patients requiring hospital admition and intensive care treatment will significantly burden the health care system in all countries. Several intensive and critical care protocols, based on the first experiences in treatment of viral pneumonia and severe COVID-19 illness, have already been published. Here we present the first version of a suggested protocol in our country, with an attached flowchart for the initial management of the COVID-19 patients in need for mechanical ventilation. The protocol is based on the worldwide existing experience in treatment of COVID-19 patients. The intention is not to replace the clinical experience and critical judgment of the attending doctors, but to strengthen their decisions and tailor treatment according to the recourses existing in our country.

The main feature of the SARS CoV-2 virus pandemic is the collapse of the health care system due to a large number of patients. This situation requires strict perioperative control of the infection to suppress the transmission of pathogens among surgical patients. Reduction of residual contamination of the working environment requires a combination of deep cleaning with disinfectants and ultraviolet C radiation. Intubation is a high-risk procedure for virus transmission and demands rigorous respect of personal protection for anesthesia providers, including a protective mask (FFP 2, FFP3), two pairs of gloves ("double gloves technique") and goggles, and disinfectant near the anesthesiology team. The workspace needs pre-planning and control of the movement through the so-called "green" and "red" zones. Before surgery, maintaining of patient's hygiene is important - including hair and body washing with antiseptic skin cleanser gel, rinse of the oral and nasal cavity and hand washing. During preoperative preparation, identification of COVID-19 infection is necessary. If the patient is febrile and the test results show the existence of a lung infection, SpO2 ≤ 90% of unknown cause and the operation is not urgent, the anesthesiologist should inform the patient, family, and surgeon that the operation should be postponed. If the patient is tested positive for SARS-CoV-2, elective surgery is delayed until the complete recovery of the patient, which includes a negative test and recovery from COVID-19. Patient should recover in the operating room after extubation. The surgical mask should be placed over an oxygen mask. Patient is transported with a surgical mask on his face to the ward directly.

SARS-CoV-2 virus causes COVID-19, which is characterized by a high level of aerosol spreading of viral particles. Aerosol generating procedures are high-risk procedures for anesthesiologists and necessities expensive high level protective personal equipment (PPE) (level 3). The problem with COVID-19 is the high number of patients, which presents an economic burden for the health care system and country, and causes issues with human and equipment resources. Airway protocols vary among hospitals like three gloves technique, videolaryngoscope, FFP3 masks, eye protection, and additional shield. All parts of the anesthesiologist's body need to be covered with protective equipment. Extubation is also considered as high risk from the point of aerosol production, and PPE level 3 is required. Patient monitoring for early warning signs leads to intubation, which is predicted and planned. The patient is preoxygenated, fully relaxed, without mask ventilation as rapid sequence intubation. The suggested time for intubation is 30 s, immediate cuff inflation, followed by a tube connecting with the machine for mechanical ventilation. Capnography serves for the tracheal intubation confirmation. Supraglottic devices and cryccothyteothomy are reserved for situation can't intubate-can't oxygenate. Airway procedures are considered as high-risk procedure, and the most experienced anesthesiologist should perform them in the shortest possible time. The best solution is to have an airway dedicated team, educated in simulation center for this specifiec type of intubation, proper planning, prepared and checked medications and equipment.

Background/Aim. Gram-positive and Gram-negative bacteria may induce different inflammatory patterns. The aim of this study was to examine the association of the myeloid-derived suppressor cells (MDSCs) with the type of infecting microorganisms (Gram positive, Gram negative, polymicrobial) and underlying cause of secondary sepsis (peritonitis, pancreatitis, trauma). Methods. Totally, 40 critically ill patients with secondary sepsis were enrolled in the prospective study. Two patients without documented positive blood culture were excluded. We detected and enumerated both main subsets of MDSCs: granulocytic (G)-MDSCs and monocytic (M)-MDSCs on the Days 1 and 5. Blood was simultaneously drawn for a blood culture. The patients with different underlying causes of sepsis (peritonitis, pancreatitis, trauma) were perceived as separated groups and the frequencies and absolute numbers of their G-MDSCs and M-MDSCs were compared. Results. Both main MDSC subpopulations were accumulated significantly in Grampositive sepsis. Univariate logistic regression analyses of investigated variables regarding Gram-positive sepsis on the Day 5 revealed that G-MDSCs absolute number along with both MMDSCs frequency and absolute number had statistically significant power for predicting Gram-positive sepsis. Stepwise multivariate logistic regression analyses of the variables on the Day 5 determined that M-MDSCs absolute number was independent predictor of Gram-positive sepsis [odds ratio (OR) 1.012; p < 0.05]. Clinical accuracy of neutrophil (Ne)/GMDSCs (Ne/G-MDSCs) and monocyte (Mo)/M-MDSCs (Mo/M-MDSCs) ratios in predicting nature of bacteremia and outcome were investigated. Discriminative power of both Ne/G-MDSCs and Mo/M-MDSCs ratios in predicting Grampositive blood culture was statistically significant both on the Day 1 and Day 5 [areas under curve (AUCs): 0.684 and 0.692, and 0.707 and 0.793, respectively). Ne/G-MDSCs both on the Day 1 and Day 5 were statistically significant predictors of lethal outcome (AUCs: 0.694 and 0.678, respectively). There were no statistically significant differences in G-MDSCs and M-MDSCs among different three groups of patients regarding peritonitis, pancreatitis and trauma as causes of sepsis neither on the Day 1 nor on the Day 5. Conclusion. Gram-positive infectious agents were powerful inducers of MDSCs generation in sepsis. Also, underlying causes of secondary sepsis might not seem to influence the MDSCs accumulation.

Background/Aim. Role of myeloid-derived suppressor cells (MDSCs) in human host response to sepsis still needs to be clarified. The aim of our study was to determine whether frequency and/or absolute numbers of the MDSCs were associated with outcome in critically ill patients with secondary sepsis and/or septic shock. Methods. Total of 40 critically ill patients with secondary sepsis were enrolled in a prospective study. We detected and enumerated both main subsets of MDSCs: granulocytic (G)-MDSCs and monocytic (M)- MDSCs on the Day 1 (the day of hospital admission) and the Day 5 after the. The primary end-point was hospital mortality. Results. Increased frequencies and absolute numbers of subpopulations corresponding to MDSCs were associated with poor outcome. As far as relative kinetics was concerned, in both survivors and non-survivors, sepsis duration from 1th to 5th day was accompanied by an increase in MDSCs values of both investigated subpopulations. In contrast to findings of stepwise multivariate logistic regression analysis of the variables on the Day 1, on the Day 5 it was determined that the Sequential Organ Failure Assessment (SOFA) score (OR 2.350; p < 0.05) and G-MDSCs frequencies (OR 3.575; p < 0.05) were independent predictors of lethal outcome. Conclusion. These findings suggest harmful role of MDSCs in secondary sepsis.

Background/Aim. Acute appendicitis (AA) is the most frequent emergency and appendectomy is the most frequent abdominal operation in the pediatric surgery. Diagnosis of AA in children is more difficult due to a lack of cooperation and poor clinical history data, leading to significant number of misdiagnostic cases. Our aim was to explore whether neutrophil to lymphocyte ratio (NLR) may be useful in diagnosis and follow-up of AA in children. Methods. Prospective investigation of NLR values in 129 consecutive patients admitted to the Mother and Child Healthcare Institute of Serbia and referred for surgery due to AA was performed. According to the pathohistological findings, patients were divided into 3 groups: normal/early, uncomplicated (phlegmonous) and complicated (gangrenous or/and perforated) AA. Laboratory analysis was done preoperativly and on the 1st and the 3rd postoperative days. Results. Statistically significant differences of NLR values were found in the different time points in total of patients and per groups. Some statistically significant differences of NLR values among histopathological groups were recorded. Investigations of correlation of NLR and other laboratory and clinical parameters showed strong positive correlation between NLR and C-reactive protein postoperatively and between NLR and Pediatric Appendicitis Score (PAS) preoperatively. Strong negative correlation with preoperative symptoms duration (PSD) were also present. Optimal cutoff NLR value between negative and positive appendectomies was 6.14. Conclusion. NLR provides well monitoring of progression of AA in children and, its cutoff values may help in distinguishing the phases of AA. Because of that, NLR should be used in diagnosis of AA in children.

Background/Aim. Because patients in intensive care units usually have an urinary catheter, the risk of urinary tract infection for these patients is higher than in other patients. The aim of this study was to identify risk factors and causative microrganisms in patients with catheter-associated urinary tract infection (CAUTI) in the Surgical Intensive Care Unit (SICU) during a 6-year period. Methods. All data were collected during prospective surveillance conducted from 2006 to 2011 in the SICU, Military Medical Academy, Belgrade, Serbia. This case control study was performed in patients with nosocomial infections recorded during surveillance. The cases with CAUTIs were identified using the definition of the Center for Disease Control and Prevention. The control group consisted of patients with other nosocomial infections who did not fulfill criteria for CAUTIs according to case definition. Results. We surveyed 1,369 patients representing 13,761 patient days. There were a total of 226 patients with nosocomial infections in the SICU. Of these patients, 64 had CAUTIs as defined in this study, and 162 met the criteria for the control group. Multivariate logistic regression analysis identified two risk factors independently associated to CAUTIs: the duration of having an indwelling catheter (OR = 1.014; 95% CI 1.005-1.024; p = 0.003) and female gender (OR = 2.377; 95%CI 1.278-4.421; p = 0.006). Overall 71 pathogens were isolated from the urine culture of 64 patients with CAUTIs. Candida spp. (28.2%), Pseudomonas aeruginosa (18.3%) and Klebsiella spp. (15.5%) were the most frequently isolated microorganisms. Conclusions. The risk factors and causative microrganisms considering CAUTIs in the SICU must be considered in of planning CAUTIs prevention in this setting.

Bacground/Aim. Using omega-3 polyunsaturated fatty acids (PUFAs) in coronary artery bypass graft surgery (CABG) could provide protection against ischemicreperfusion damage, prevention of postoperative arrhythmia and attenuation of inflammatory response. However, omega-3 PUFAs inhibit cyclooxygenase (and thus decrease the synthesis of thromboxane A2 from arachidonic acid in platelets), which leads to decreased platelet aggregation. In cardiac surgery it is necessary to achieve a balance between inhibition and full platelets function. It is as well as important to closely follow hematological parameters, impaired by CABG itself. Therefore, the aim of the study was to establish the effects of pretreatment with omega- PUFAs on hematological parameters and plateletes aggregation in patients with elective CABG. Methods. This prospective, randomized, placebo-controlled, single-center trial was performed on parallel groups. The patients (n = 40) undergoing elective CABG were randomized receiving preoperative intravenous omega-3 PUFAs (Omegaven® 10%) infusion (the PUFAs group) or the same volume of 0.9% saline solution infusion (the control group). Infusion was given a day before surgery and repeated four hours before starting extracorporeal circulation (CPB) via the peripheral vein at single doses of 100 mL (25 mL/h). Platelet function analysis was performed using multiple electrode aggregometry (MEA, multiplate-analyzer) before starting CPB and 2 h postoperatively for the patients of both groups. Results. There were no clinically relevant differences in baseline characteristics between the groups. Hematological parameters were not significantly different between the groups pre-, intra- and postoperatively. During the first 24 h after surgery, the loss of blood was similar in the PUFAs and the control group (680 ± 274 mL and 608 ± 210 mL, respectively; p = 0.356). Postoperatively, platelet aggregation was not significantly different between the PUFAs and the control group in adenosine diphosphate (ADP) test (39 ± 11 and 42 ± 15, respectively; p = 0.701), arachidonic acid (ASPI) test (64 ± 24 and 70 ± 27, respectively; p = 0.525) and trombin receptor-activating peptide (TRAP) test (68 ± 25 and 75 ± 26, respectively; p = 0.396), while their aggregation in collagen (COL) test was statistically significantly lower in the PUFAs related to the control group (32 ± 15 and 47 ± 20, respectively; p = 0.009). Conclusion. Acute pretreatment with omega-3 PUFAs insignificantly affected the activity of platelets and did not influence postoperative blood loss.

We investigated effects of total intravenous anesthesia (TIVA) with propofol and remifentanil (in two parallel continuous infusions), on 28 ASA I-II patients undergoing laparoscopic cholecystectomy. All patients received midazolame (0.05 mg/kg b.w.), and 90 sec thereafter, remifentanil (0.5 g/kg b.w.). Computer controlled intravenous infusion of propofol started at dose of 6 mg/kg/h (by Graseby 3400 Syringe Pump). Muscle relaxation was achieved by rocuronium (0.6 mg/kg b.w.). After endotracheal intubation, rate of propofol was decreased on 3 mg/kg/h and started with another infusion of remifentanil (0.5 ug/kg/min). Before (T0) and after induction (T1), after start of surgery (T2), and at the end of surgery (T3), we evaluated: systolic, diastolic, and medial arterial blood pressure (SAP, DAP, MAP), heart rate (HR), peripheral saturation of O2 (O2Sat), and capnometry (ETCO2), by Datex-Engstrome AS/3 Monitore. It was followed side effects of anaesthesia, early and complete recovery rate, and frequency of nausea and vomiting in postoperative period. Results showed haemodynamic stability of patients after induction in anaesthesia (defined as decreasing of MAP 20%, compared with preinduction values). During investigation (T0-T3), results of 0.2Sat and ETCO2 were excellent (0.60 +/- 2 and 5.1 +/- 2.4 min). There wasonly one case of postoperative nausea and vomiting, and no significant side effects of anaesthesia. TIVA remifentanil-propofol and co-induction with midazolame makes possible haemodynamic stability of patients after induction in anaesthesia, good oxygenation during surgery, fast early and complete recovery, and avoiding of side effects of anaesthesia and postoperative nausea and vomiting. We concluded that it is a good choice of anaesthesia for laparoscopic cholecystectomy.

On a large pig farm with a known history of necrotic enteritis 12 pregnant gilts were vaccinated s. c. 7 and 2 weeks before expected farrowing with a commercial bacterin-toxoid preparation of toxigenic strains C. perfringens type C and D (DizevakR-Pliva, Zagreb). At the farrowing the titers of beta-antitoxins in serum samples from vaccinated gilts ranged from 9.0 to 26.0 IU/ml with a mean value of 14.16 IU/ml. Colostral titers varied from 12.0 IU/ml with a mean of 16.12 IU/ml. On the second day of life the mean serum titers between litters differed greatly from 4.75 to 24.0 IU/ml. By the age of 7 days the average serum titers were commonly lower and varied between the litters from 2.25 to 15.0 IU/ml, with a low of 1.5 to a high of 16.0 IU/ml in single animals. Ten (8.47%) out of a total of 118 piglets from vaccinated gilts died during the first 7 days of life but the losses were not caused by C. perfringens infection. In unvaccinated control animals 18 (15.9%) of 113 piglets died, eleven of them with clinical and pathoanatomical signs of necrotic enteritis. The affected piglets predominantly succumbed in the first 4 days of life. These data indicate that the investigated bacterin-toxoid can be successfully used in immunoprophylaxis of necrotic enteritis in piglets.

The dopamine agonist bromocriptine and L-dopa significantly inhibited whereas dopamine antagonist haloperidol aggravated the gastric lesions induced by pylorus ligation in mice as found earlier for rats. Furthermore, the successful use of a dopamine antagonist alone for the induction of gastric lesions also in mice was demonstrated, since the gastric lesions were induced by a single dose of haloperidol without any additional noxious treatment. Bromocriptine successfully inhibited both the gastric lesion-potentiating as well as the gastric lesion-inducing effect of haloperidol.

The influence of the dopamine receptor-stimulating agent, bromocriptine, the dopamine-releasing drug, amantadine, and the dopamine antagonist, domperidone, on acute pancreatitis was studied in rats. Acute pancreatitis was induced by ligation of the bile duct at its point of entry into the duodenum. Each drug was applied intraperitoneally 1 h before induction of acute pancreatitis and all the surviving animals were killed 24 h thereafter. The control, saline-pretreated animals exhibited the mortality rate, macroscopical and histological changes, as well as increase of serum amylase levels that were consistent with acute pancreatitis. Domperidone induced a large increase in serum amylase which was significantly reduced by the simultaneous administration of bromocriptine. However, both bromocriptine and amantadine, when given separately did not prevent the increase of serum amylase levels to the control levels. Statistical analysis showed that the difference between the mortality rate in the control and treated groups did not reach the level of significance probably due to the rather limited number of animals used. On the other hand, application of bromocriptine as well as amantadine successfully reduced the onset of acute pancreatitis whereas domperidone, a rather specific peripheral dopamine receptor blocker, had the opposite effect. Both bromocriptine and amantadine significantly reduced the mortality rate from acute pancreatitis in domperidone-pretreated rats. Since the aggravating effect of domperidone was successfully reduced by simultaneous application of bromocriptine, we think that these effects are mediated by peripheral dopamine receptors. However, the mechanisms whereby dopamine receptor-stimulating and dopamine-releasing drugs produce their beneficial effects remain to be elucidated.

Dopamine agents (saline in control groups) were coadministered with indomethacin by either single or repeated application. The ulcerogenic effect (erosions and/or ulcers) of repeated given indomethacin on gastric mucosa differed clearly from that on intestinal mucosa. The effect on intestinal mucosa was markedly greater than after a single dose. The effects of dopamine agents appeared to be more consistent. Domperidone and haloperidol, given as single or repeated doses, strongly aggravated both the gastric and intestinal lesions. Bromocriptine and amantadine had a protective effect. The adverse effects of both dopamine antagonists (increased after repeated administration) were strongly inhibited by the simultaneous administration of either bromocriptine or amantadine. The involvement of the dopamine system (central or peripheral) in the mechanisms that maintain gastric (probably related to cytoprotection also) and intestinal mucosa integrity is therefore suggested.