Prediction of a Difficult Airway Using the ARNE Score and Flexible Laryngoscopy in Patients with Laryngeal Pathology.

Background and Objectives: The ARNE score was developed for the prediction of a difficult airway for both general and ear, nose and throat (ENT) surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight into its effects in combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We calculated the ARNE score for every patient, and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to the intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to the IDS. The ARNE score showed limited accuracy for the prediction of difficult intubation in laryngology with p < 0.0001 and an AUC of 0.784. Flexible laryngoscopy also showed limitations when used as an independent parameter with p < 0.0001 and an AUC of 0.766. We defined a new cut-off value of 15.50 for laryngology, according to the AUC. After the patients were divided into two groups, according to the new cut-off value and provided cut-off value, the AUC improved to 0.707 from 0.619, respectively. Flexible laryngoscopy improved the prediction model of the ARNE score to an AUC of 0.882 and of the new cut-off value to an AUC of 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with the ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, the universally recommended cut-off value of 11 cannot be effectively used in laryngology, and a new cut-off value of 15.50 is recommended.

From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?

Complex immune response to infection has been highlighted, more than ever, during the COVID-19 pandemic. This review explores the immunomodulatory treatment of moderate-to-severe forms of this viral sepsis in the context of specific immunopathogenesis. Our objective is to analyze in detail the existing strategies for the use of immunomodulators in COVID-19. Immunomodulating therapy is very challenging; there are still underpowered or, in other ways, insufficient studies with inconclusive or conflicting results regarding a rationale for adding a second immunomodulatory drug to dexamethasone. Bearing in mind that a "cytokine storm" is not present in the majority of COVID-19 patients, it is to be expected that the path to the adequate choice of a second immunomodulatory drug is paved with uncertainty. Anakinra, a recombinant human IL-1 receptor antagonist, is a good choice in this setting. Yet, the latest update of the COVID-19 Treatment Guidelines Panel (31 May 2022) claims that there is insufficient evidence to recommend either for or against the use of anakinra for the treatment of COVID-19. EMA's human medicines committee recommended extending the indication of anakinra to include treatment of COVID-19 in adult patients only recently (17 December 2021). It is obvious that this is still a work in progress, with few ongoing clinical trials. With over 6 million deaths from COVID-19, this is the right time to speed up this process. Our conclusion is that, during the course of COVID-19, the immune response is changing from the early phase to the late phase in individual patients, so immunomodulating therapy should be guided by individual responses at different time points.

Immunomonitoring of Monocyte and Neutrophil Function in Critically Ill Patients: From Sepsis and/or Trauma to COVID-19.

Immune cells and mediators play a crucial role in the critical care setting but are understudied. This review explores the concept of sepsis and/or injury-induced immunosuppression and immuno-inflammatory response in COVID-19 and reiterates the need for more accurate functional immunomonitoring of monocyte and neutrophil function in these critically ill patients. in addition, the feasibility of circulating and cell-surface immune biomarkers as predictors of infection and/or outcome in critically ill patients is explored. It is clear that, for critically ill, one size does not fit all and that immune phenotyping of critically ill patients may allow the development of a more personalized approach with tailored immunotherapy for the specific patient. In addition, at this point in time, caution is advised regarding the quality of evidence of some COVID-19 studies in the literature.

Possible cytokine biomarkers in pediatric acute appendicitis.

BACKGROUND: Diagnosis of acute appendicitis (AA) and decisions about its treatment remain among the most common dilemmas of pediatric surgical teams. Monitoring of immune response may be of importance for this purpose. Our aim was to measure and analyze serum and peritoneal fluid cytokines, in children who had undergone surgery for suspected AA. METHODS: Prospective investigation of serum and peritoneal fluid cytokine values was performed in 127 consecutive patients. According to the pathohistological findings, patients were divided into three groups: normal/early, uncomplicated and complicated AA. Determination of cytokine concentrations for 20 different cytokines was done using a commercial flow cytometry kit: Human Inflammation 20 plex BMS 819. RESULTS: Statistically significant differences in serum cytokine values between pathohistological groups were found for IP-10, MIP-1α and IL-10. Preoperative cut-off values of IP-10, MIP-1α and IL-10 between groups were obtained using ROC curve analysis. Positive correlations between serum and peritoneal concentrations were recorded for most of the analyzed cytokines. CONCLUSION: IP-10, MIP-1α and IL-10 showed potential in assessment of AA in children. Confirmatory studies with a larger number of patients are required to prove reliability of these biomarkers.

Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count (MPV/PC) ratio are readily available parameters that might have discriminative power regarding outcome. The aim of our study was to assess prognostic value of these biomarkers regarding outcome in critically ill patients with secondary sepsis and/or trauma. METHODS: A total of 392 critically ill and injured patients, admitted to surgical ICU, were enrolled in a prospective observational study. Leukocyte and platelet counts were recorded upon fulfilling Sepsis-3 criteria and for traumatized Injury Severity Score > 25 points. Patients were divided into four subgroups: peritonitis, pancreatitis, trauma with sepsis, and trauma without sepsis. RESULTS: NLR and MPV/PC levels were significantly higher in nonsurvivors (AUC/ROC of 0.681 and 0.592, resp., in the peritonitis subgroup; 0.717 and 0.753, resp., in the pancreatitis subgroup); MLR and PLR did not differ significantly. There was no significant difference of investigated biomarkers between survivors and nonsurvivors in trauma patients with and without sepsis except for PLR in the trauma without sepsis subgroup (significantly higher in nonsurvivors, AUC/ROC of 0.719). Independent predictor of lethal outcome was NLR in the whole cohort and in the peritonitis subgroup as well as MPV in the pancreatitis subgroup. Also, there were statistically significant differences in MPV/PC, MLR, and PLR values regarding nature of bacteremia. In general, the lowest levels had been found in patients with Gram-positive blood cultures. CONCLUSIONS: NLR and MPV were very good independent predictors of lethal outcome. For the first time, we demonstrate that nature of bacteremia influences MPV/PC, MLR, and PLR. In heterogeneous cohort subgroup, analysis is essential.

Efficacy of external warming in attenuation of hypothermia in surgical patients.

BACKGROUND/AIM: Hypothermia in surgical patients can be the consequence of long duration of surgical intervention, general anaesthesia and low temperature in operating room. Postoperative hypothermia contributes to a number of postoperative complications such as arrhythmia, myocardial ischemia, hypertension, bleeding, wound infection, coagulopathy, and prolonged effect of muscle relaxants. External heating procedures are used to prevent this condition. The aim of this study was to evaluate the efficiency of external warming system in alleviation of cold stress and hypothermia in patients who underwent major surgical procedures. METHODS: The study was conducted in the Military Medical Academy in Belgrade. A total of 30 patients of both genders underwent abdominal surgical procedures, randomly divided into two equal groups: the one was externally warmed using warm air mattress (W), while in the control group (C) surgical procedure was performed in regular conditions, without additional warming. Oesophageal temperature (Te) was used as indicator of changes in core temperature, during surgery and awakening postoperative period, and temperature of control sites on the right hand (Th) and the right foot (Tf) reflected the changes in skin temperatures during surgery. Te and skin temperatures were monitored during the intraoperative period, with continuous measurement of Te during the following 90 minutes of the postoperative period. Heart rates and blood pressures were monitored continuously during the intraoperative and awakening period. RESULTS: In the W group, the average Te, Tf and Th did not change significantly during the intraoperative as well as the postoperative period. In the controls, the average Te significantly decreased during the intraoperative period (from 35.61 ± 0.35 °C at 0 minute to 33.86 ± 0.51°C at 120th minute). Compared to the W group, Te in the C group was significantly lower in all the observed periods. Average values of Tf and Th significantly decreased in the C group (from 30.83 ± 1.85 at 20th minute to 29.0 ± 1.39°C at 120th minute, and from 32.75 ± 0.96 to 31.05 ± 1.09°C, respectively). CONCLUSION: The obtained results confirm that the external warming using warm air mattress was able to attenuate hypothermia, i.e. substantial decrease in core temperature, compared with the similar exposure to cold stress in the control group.

Cytokine profile in severe Gram-positive and Gram-negative abdominal sepsis.

Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-ß1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors.

Prognostic Value and Daily Trend of Interleukin-6, Neutrophil CD64 Expression, C-Reactive Protein and Lipopolysaccharide-Binding Protein in Critically Ill Patients: Reliable Predictors of Outcome or Not?

BACKGROUND: Severe sepsis and/or trauma complicated by multiple organ dysfunction syndrome are the leading causes of death in critically ill patients. The aim of this prospective single-centre study was to assess the prognostic value and daily trend of interleukin-6 (IL-6), neutrophil CD64 expression, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) regarding outcome in critically ill patients with severe trauma and/or severe sepsis. Outcome measure was hospital mortality. METHODS: One hundred and two critically ill patients admitted to the intensive care unit of a tertiary university hospital were enrolled in this prospective study. Blood samples were collected on admission (day 1), days 2 and 3. RESULTS: CD64 index was 1.6-fold higher on day 1 and 1.78-fold higher on day 2 in non-survivors (p<0.05). The area under the curve (AUC) for the CD64 index on day 1 for outcome was 0.727. At a cut-off level of 2.80 sensitivity was 75% and specificity was 65%. Patients with CD64 index level on day 1 higher than 2.80 had 2.4-fold higher probability of dying. Odds ratio is 2.40; 95% CI 0.60-9.67. CONCLUSIONS: CD64 index on day 1 is a fairly good predictor of outcome. AUCs for IL-6, CRP and LBP were < 0.55, suggesting these biomarkers failed to predict outcome.

Factors influencing antibiotic treatment cost and outcome in critically ill patients: a "real-life" study.

UNLABELLED: BACKGROUND/AIM. Critically ill patients are at very high risk of developing severe infections in intensive care units (ICUs). Procalcitonin (PCT) levels are eleveted in the circulation in patients with bacterial sepsis and PCT might be useful in guiding antibiotic treatment. The aim of this study was to estimate factors influencing patients survival and treatment cost in ICU with special emphasis on the impact of PCT serum levels use in guiding antimicrobial therapy. METHODS: The study was conducted from August 2010 to May 2012 in the Intensive Therapy Unit, Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy (MMA), Belgrade, Serbia. All adult critically ill patients with sepsis and/or trauma admitted in the ICU were included in the study. This study included only the cost of antimicrobial therapy in the ICU and the cost for PCT analysis. We used prices valid in the MMA for the year 2012. PCT in serum was measured by homogeneous immunoassay on a Brahms Kryptor analyzer. RESULTS: A total of 102 patients were enrolled. The mean patients age was 55 ± 19 years and 61.8% of patients were male. The mean length of stay (LOS) in the ICU was 12 ± 21 days. There was a statistically significant difference (p < 0.001) between the sepsis and trauma group regarding outcome (higher mortality rate was in the sepsis group, particularly in the patients with peritonitis who were mostly women). The patients younger than 70 years had better chance of survival. LOS, the use of carbapenems and PCT-measurement influenced the cost of therapy in the ICU. CONCLUSIONS: The obtained results show that age, the diagnosis and gender were the main predictors of survival of critically ill patients in the ICU. The cost of ICU stay was dependent on LOS, use of carbapenems and PCT-measurement although the influence of these three factors on the outcome in the patients did not reach a statistical significance.

Immunoinflammatory response in critically ill patients: severe sepsis and/or trauma.

Immunoinflammatory response in critically ill patients is very complex. This review explores some of the new elements of immunoinflammatory response in severe sepsis, tumor necrosis factor-alpha in severe acute pancreatitis as a clinical example of immune response in sepsis, immune response in severe trauma with or without secondary sepsis, and genetic aspects of host immuno-inflammatory response to various insults in critically ill patients.

Immune response in severe infection: could life-saving drugs be potentially harmful?

Critically ill patients suffer a high rate of nosocomial infection with secondary sepsis being a common cause of death. Usage of antibiotics and catecholamines is often necessary, but it can compromise complex immune response to infection. This review explores influence of these life-saving drugs on host immune response to severe infection.

The effects of acclimatization on blood clotting parameters in exertional heat stress.

BACKGROUND/AIM: Exertional heat stress is a common problem in military services. Considering the coagulation abnormalities are of major importance in development of severe heat stroke, we wanted to examine changes in hemostatic parameters in soldiers during exertional heat stress test as well as the effects of a 10-day passive or active acclimatization in a climatic chamber. METHODS: A total of 40 male soldiers with high aerobic capacity performed exertional heat stress test (EHST) either in cool [20 degrees C, 16 degrees C wet bulb globe temperature (WBGT)], or hot (40 degrees C, 29 degrees C, (WBGT) environment, unacclimatized (U) or after 10 days of passive (P) or active (A) acclimatization. Physiological strain was measured by tympanic temperatures (Tty) and heart rates (HR). Platelet count (PC), antithrombin III (AT), and prothrombin time (PT) were assessed in blood samples collected before and immediately after the EHST. RESULT: EHST in hot conditions induced physiological heat stress (increase in Tty and HR), with a significant increase in prothrombin time in the groups U and A. Platelet counts were significantly higher after the EHST compared to the basic levels in all the investigated groups, regardless environmental conditions and acclimatization state. Antithrombin levels were not affected by EHST whatsoever. CONCLUSION: In the trained soldiers, physiological heat stress caused mild changes in some serum parameters of blood clotting such as prothrombin time, while others such as antithrombin levels were not affected. Platelet counts were increased after EHST in all groups. A 10-day passive or active acclimatization in climatic chamber showed no effect on parameters investigated.

Tumor necrosis factor-α levels early in severe acute pancreatitis: is there predictive value regarding severity and outcome?

GOAL AND BACKGROUND: One of the most important cytokines in pathogenesis of acute pancreatitis is tumor necrosis factor (TNF)-α. The aim of our study was to determine whether the plasma levels of TNF-α in patients with severe acute pancreatitis (SAP) on admission correlate with severity and outcome of SAP. STUDY: Blood samples were obtained from 100 patients with SAP. Patients were divided into 2 groups according to severity: SAP group (n=69) and SAP-induced multiple organ dysfunction syndrome (MODS) group (n=31). Survivors were patients who were alive 90 days after taking the blood sample for cytokine measurement (53/100). Blood sample for cytokine measurement was drawn immediately after admission. TNF-α was measured by commercial ELISA test in plasma. RESULTS: When comparing SAP group with SAP-induced MODS group, we found that mean values of TNF-α on admission were 191.5-fold lower in group with SAP-induced MODS (P<0.01). When comparing nonsurvivors with survivors, we found that mean values of TNF-α on admission were 63-fold higher in survivors (P<0.01). At cut-off level of 7.95 pg/mL sensitivity was 83.9% and specificity was 72.5%. Patients with TNF-α level lower than 7.95 pg/mL had 3.2-fold higher probability to develop SAP with MODS. At cut-off level of 10.5 pg/mL sensitivity was 83% and specificity was 77.4%. Patients with TNF-α level higher than 10.5 pg/mL had 4.8-fold higher probability to survive. CONCLUSIONS: TNF-α is good predictor of severity and outcome. Low TNF-α concentration in patients with SAP predicts development of MODS and fatal outcome.

[Effect of mechanical pressure-controled ventilation in patients with disturbed respiratory function during laparoscopic cholecystectomy].

BACKGROUND/AIM: Laparoscopic cholecystectomy is considered to be the gold standard for laparoscopic surgical procedures. In ASA III patients with concomitant respiratory diseases, however, creation of pneumoperitoneum and the position of patients during surgery exert additional negative effect on intraoperative respiratory function, thus making a higher challenge for the anesthesiologist than for the surgeon. The aim of this study was to compare the effect of intermittent positive pressure ventilation (IPPV) and pressure controlled ventilation (PCV) during general anesthesia on respiratory function in ASA III patients submitted to laparoscopic cholecystectomy. METHODS: The study included 60 patients randomized into two groups depending on the mode of ventilation: IPPV or PCV. Respiratory volume (VT), peak inspiratory pressure (PIP), compliance (C), end-tidal CO2 pressure (PETCO2), oxygen saturation (SpO2), partial pressures of O2, CO2 (PaO2 and PaCO2) and pH of arterial blood were recorded within four time intervals. RESULTS: There were no statistically significant differences in VT, SpO2, PaO2, PaCO2 and pH values neither within nor between the two groups. In time interval t1 there were no statistically significant differences in PIP, C, PETCO2 values between the IPPV and the PCV group. But, in the next three time intervals there was a difference in PIP, C, and PETCO2 values between the two groups which ranged from statistically significant to highly significant; PIP was lower, C and PETCO2 were higher in the PCV group. CONCLUSION: Pressure controlled ventilation better maintains stability regarding intraoperative ventilatory parameters in ASA III patients with concomitant respiratory diseases during laparoscopic cholecystectomy.