Early empiric antibiotic use in COVID-19 patients: results from the international VIRUS registry.

OBJECTIVES: COVID-19 escalated inappropriate antibiotic use. We determined the distribution of pathogens causing community-acquired co-infections, the rate, and factors associated with early empiric antibiotic (EEAB) treatment among hospitalized COVID-19 patients. METHODS: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry including 68,428 patients from 28 countries enrolled between January 2020 and October 2021 were screened. After exclusions, 7830 patients were included in the analysis. Azithromycin and/or other antibiotic treatment given within the first 3 days of hospitalization was investigated. Univariate and multivariate analyses were performed to determine factors associated with EEAB use. RESULTS: The majority (6214, 79.4%) of patients received EEAB, with azithromycin combination being the most frequent (3146, 40.2%). As the pandemic advanced, the proportion of patients receiving EEAB regressed from 84.4% (786/931) in January-March 2020 to 65.2% (30/46) in April-June 2021 (P < 0.001). Beta-lactams, especially ceftriaxone was the most commonly used antibiotic. Staphylococcus aureus was the most commonly isolated pathogen. Multivariate analysis showed geographical location and pandemic timeline as the strongest independent predictors of EEAB use. CONCLUSIONS: EEAB administration decreased as pandemic advanced, which may be the result of intensified antimicrobial stewardship efforts. Our study provides worldwide goals for antimicrobial stewardship programs in the post-COVID-19 era.

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019.

BACKGROUND: Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. METHODS: This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. RESULTS: Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. CONCLUSION: Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

Discharge Disposition and Loss of Independence Among Survivors of COVID-19 Admitted to Intensive Care: Results From the SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS).

OBJECTIVES: To describe incidence and risk factors of loss of previous independent living through nonhome discharge or discharge home with health assistance in survivors of intensive care unit (ICU) admission for coronavirus disease 2019 (COVID-19). DESIGN: Multicenter observational study including patients admitted to the ICU from January 2020 till June 30, 2021. HYPOTHESIS: We hypothesized that there is a high risk of nonhome discharge in patients surviving ICU admission due to COVID-19. SETTING: Data were included from 306 hospitals in 28 countries participating in the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 registry. PATIENTS: Previously independently living adult ICU survivors of COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was nonhome discharge. Secondary outcome was the requirement of health assistance among patients who were discharged home. Out of 10 820 patients, 7101 (66%) were discharged alive; 3791 (53%) of these survivors lost their previous independent living status, out of those 2071 (29%) through nonhome discharge, and 1720 (24%) through discharge home requiring health assistance. In adjusted analyses, loss of independence on discharge among survivors was predicted by patient age ≥ 65 years (adjusted odds ratio [aOR] 2.78, 95% confidence interval [CI] 2.47-3.14, P < .0001), former and current smoking status (aOR 1.25, 95% CI 1.08-1.46, P = .003 and 1.60 (95% CI 1.18-2.16), P = .003, respectively), substance use disorder (aOR 1.52, 95% CI 1.12-2.06, P = .007), requirement for mechanical ventilation (aOR 4.17, 95% CI 3.69-4.71, P < .0001), prone positioning (aOR 1.19, 95% CI 1.03-1.38, P = .02), and requirement for extracorporeal membrane oxygenation (aOR 2.28, 95% CI 1.55-3.34, P < .0001). CONCLUSIONS: More than half of ICU survivors hospitalized for COVID-19 are unable to return to independent living status, thereby imposing a significant secondary strain on health care systems worldwide.

Development and Validation of an Acute Respiratory Distress Syndrome Prediction Model in Coronavirus Disease 2019: Updated Lung Injury Prediction Score.

OBJECTIVE: To develop and validate an updated lung injury prediction score for coronavirus disease 2019 (COVID-19) (c-LIPS) tailored for predicting acute respiratory distress syndrome (ARDS) in COVID-19. PATIENTS AND METHODS: This was a registry-based cohort study using the Viral Infection and Respiratory Illness Universal Study. Hospitalized adult patients between January 2020 and January 2022 were screened. Patients who qualified for ARDS within the first day of admission were excluded. Development cohort consisted of patients enrolled from participating Mayo Clinic sites. The validation analyses were performed on remaining patients enrolled from more than 120 hospitals in 15 countries. The original lung injury prediction score (LIPS) was calculated and enhanced using reported COVID-19-specific laboratory risk factors, constituting c-LIPS. The main outcome was ARDS development and secondary outcomes included hospital mortality, invasive mechanical ventilation, and progression in WHO ordinal scale. RESULTS: The derivation cohort consisted of 3710 patients, of whom 1041 (28.1%) developed ARDS. The c-LIPS discriminated COVID-19 patients who developed ARDS with an area under the curve (AUC) of 0.79 compared with original LIPS (AUC, 0.74; P<.001) with good calibration accuracy (Hosmer-Lemeshow P=.50). Despite different characteristics of the two cohorts, the c-LIPS's performance was comparable in the validation cohort of 5426 patients (15.9% ARDS), with an AUC of 0.74; and its discriminatory performance was significantly higher than the LIPS (AUC, 0.68; P<.001). The c-LIPS's performance in predicting the requirement for invasive mechanical ventilation in derivation and validation cohorts had an AUC of 0.74 and 0.72, respectively. CONCLUSION: In this large patient sample c-LIPS was successfully tailored to predict ARDS in COVID-19 patients.

The Association of Latitude and Altitude with COVID-19 Symptoms: A VIRUS: COVID-19 Registry Analysis.

Background: Better delineation of COVID-19 presentations in different climatological conditions might assist with prompt diagnosis and isolation of patients. Objectives: To study the association of latitude and altitude with COVID-19 symptomatology. Methods: This observational cohort study included 12267 adult COVID-19 patients hospitalized between 03/2020 and 01/2021 at 181 hospitals in 24 countries within the SCCM Discovery VIRUS: COVID-19 Registry. The outcome was symptoms at admission, categorized as respiratory, gastrointestinal, neurological, mucocutaneous, cardiovascular, and constitutional. Other symptoms were grouped as atypical. Multivariable regression modeling was performed, adjusting for baseline characteristics. Models were fitted using generalized estimating equations to account for the clustering. Results: The median age was 62 years, with 57% males. The median age and percentage of patients with comorbidities increased with higher latitude. Conversely, patients with comorbidities decreased with elevated altitudes. The most common symptoms were respiratory (80%), followed by constitutional (75%). Presentation with respiratory symptoms was not associated with the location. After adjustment, at lower latitudes (<30º), patients presented less commonly with gastrointestinal symptoms (p<.001, odds ratios for 15º, 25º, and 30º: 0.32, 0.81, and 0.98, respectively). Atypical symptoms were present in 21% of the patients and showed an association with altitude (p=.026, odds ratios for 75, 125, 400, and 600 meters above sea level: 0.44, 0.60, 0.84, and 0.77, respectively). Conclusions: We observed geographic variability in symptoms of COVID-19 patients. Respiratory symptoms were most common but were not associated with the location. Gastrointestinal symptoms were less frequent in lower latitudes. Atypical symptoms were associated with higher altitude.

Clinical characteristics and outcomes of critically ill mechanically ventilated COVID-19 patients receiving interleukin-6 receptor antagonists and corticosteroid therapy: a preliminary report from a multinational registry.

BACKGROUND: Interleukin-6 receptor antagonists (IL-6RAs) and steroids are emerging immunomodulatory therapies for severe and critical coronavirus disease (COVID-19). In this preliminary report, we aim to describe the epidemiology, clinical characteristics, and outcomes of adult critically ill COVID-19 patients, requiring invasive mechanical ventilation (iMV), and receiving IL-6RA and steroids therapy over the last 11 months. MATERIALS AND METHODS: International, multicenter, cohort study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Data were collected between March 01, 2020, and January 10, 2021. RESULTS: Of 860 patients who met eligibility criteria, 589 received steroids, 170 IL-6RAs, and 101 combinations. Patients who received IL-6RAs were younger (median age of 57.5 years vs. 61.1 and 61.8 years in the steroids and combination groups, respectively). The median C-reactive protein level was > 75 mg/L, indicating a hyperinflammatory phenotype. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (interquartile range: 6-14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. Of the patients who received IL-6RAs, the majority received one dose of tocilizumab and sarilumab (dose range of 600-800 mg for tocilizumab and 200-400 mg for sarilumab). Regarding the timing of administration, we observed that steroid and IL-6RA administration on day 0 of ICU admission was only 55.6% and 39.5%, respectively. By day 28, when compared with steroid use alone, IL-6RA use was associated with an adjusted incidence rate ratio (aIRR) of 1.12 (95% confidence interval [CI] 0.88, 1.4) for ventilator-free days, while combination therapy was associated with an aIRR of 0.83 (95% CI 0.6, 1.14). IL-6RA use was associated with an adjusted odds ratio (aOR) of 0.68 (95% CI 0.44, 1.07) for the 28-day mortality rate, while combination therapy was associated with an aOR of 1.07 (95% CI 0.67, 1.70). Liver dysfunction was higher in IL-6RA group (p = 0.04), while the bacteremia rate did not differ among groups. CONCLUSIONS: Discordance was observed between the registry utilization patterns (i.e., timing of steroids and IL-6RA administration) and new evidence from the recent randomized controlled trials and guideline recommendations. These data will help us to identify areas of improvement in prescribing patterns and enhance our understanding of IL-6RA safety with different steroid regimens. Further studies are needed to evaluate the drivers of hospital-level variation and their impact on clinical outcomes. Trial registration ClinicalTrials.gov: NCT04486521. Registered on July 2020.

Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry.

Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID-19) patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/NCT04323787). We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (390 of 1012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1939 = 14%), presenting a risk ratio of 2.79 (95% confidence interval [CI]: [2.42, 3.16]; p = 4.45e-52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin versus 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% CI: [1.42, 2.00]; p = 1.5e-8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2644 [25%]), risk ratio 1.26 (95% CI: [1.14, 1.40]; p = 7.5e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1047 [30%] for Black/African American vs. 263 of 1047 [25%] for White/Caucasian, p = .02, risk ratio 1.18; 95% CI: [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID-19 patients.

The pathophysiology of complications after laparoscopic colorectal surgery: Role of baroreflex and chemoreflex impairment.

INTRODUCTION: The aim of this study was to assess the dynamics of baroreflex sensitivity (BRS) during laparoscopic colorectal surgery in patients with different chemoreflex sensitivity assessed with breath-holding test. METHODS: The study included 80 patients (mean age, 68 ±â€¯7 years) who underwent routine laparoscopic colorectal surgery under general/epidural anaesthesia. Patients were retrospectively divided into two groups: with normal (breath-holding duration ≥38 s, group N [n = 42]) or high (breath-holding duration <38 s, group H [n = 38]) chemoreflex sensitivity. BRS was initially evaluated after arterial catheter placement before induction, after induction, after pneumoperitoneum, after extubation, and 6 h and 24 h after extubation. RESULTS: Average BRS was significantly lower in the group with high peripheral chemoreflex sensitivity at all time points. The use of pneumoperitoneum did not significantly influence BRS in either group. After the surgery and 6 h after extubation, no significant changes were observed. After 6 h of the surgery, 11.9% of patients in group N and 57.8% of those in group H (p < 0.05) had severe baroreflex dysfunction (BRS < 3 ms/mmHg). After 24 h, only two patients in group N (vs 13 [34.2%] in group H, p < 0.05) had this dysfunction. CONCLUSION: Patients with high chemoreflex sensitivity have lower BRS, and it decreases further after anaesthesia induction. The recovery process can take up to 24 h, with an increased risk of perioperative complications in patients with high preoperative chemoreflex sensitivity. The use of pneumoperitoneum does not significantly affect BRS.

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial.

Importance: Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy. Objective: To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy. Design, Setting, and Participants: The SCARLET trial was a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study conducted in intensive care units at 159 sites in 26 countries. All adult patients admitted to one of the participating intensive care units between October 2012 and March 2018 with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, defined as an international normalized ratio greater than 1.40 without other known etiology and a platelet count in the range of 30 to 150 × 109/L or a greater than 30% decrease in platelet count within 24 hours, were considered for inclusion. The final date of follow-up was February 28, 2019. Interventions: Patients with sepsis-associated coagulopathy were randomized and treated with an intravenous bolus or a 15-minute infusion of thrombomodulin (0.06 mg/kg/d [maximum, 6 mg/d]; n = 395) or matching placebo (n = 405) once daily for 6 days. Main Outcome and Measures: The primary end point was 28-day all-cause mortality. Results: Among 816 randomized patients, 800 (mean age, 60.7 years; 437 [54.6%] men) completed the study and were included in the full analysis set. In these patients, the 28-day all-cause mortality rate was not statistically significantly different between the thrombomodulin group and the placebo group (106 of 395 patients [26.8%] vs 119 of 405 patients [29.4%], respectively; P = .32). The absolute risk difference was 2.55% (95% CI, -3.68% to 8.77%). The incidence of serious major bleeding adverse events (defined as any intracranial hemorrhage; life-threatening bleeding; or bleeding event classified as serious by the investigator, with administration of at least 1440 mL [typically 6 units] of packed red blood cells over 2 consecutive days) was 23 of 396 patients (5.8%) in the thrombomodulin group and 16 of 404 (4.0%) in the placebo group. Conclusions and Relevance: Among patients with sepsis-associated coagulopathy, administration of a human recombinant thrombomodulin, compared with placebo, did not significantly reduce 28-day all-cause mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT01598831.

Influence of a New "Call-Out Algorithm" for Management of Postoperative Pain and Its Side Effects on Length of Stay in Hospital: A Two-Centre Prospective Randomized Trial.

BACKGROUND: We recently introduced the efficacy safety score (ESS) as a new "call-out algorithm" for management of postoperative pain and side effects. In this study, we report the influence of ESS recorded hourly during the first 8 hours after surgery on the mobility degree, postoperative nonsurgical complications, and length of hospital stay (LOS). METHODS: We randomized 1152 surgical patients into three groups for postoperative observation: (1) ESS group (n = 409), (2) Verbal Numeric Rate Scale (VNRS) for pain group (n = 417), and (3) an ordinary qualitative observation (Control) group (n = 326). An ESS > 10 or VNRS > 4 at rest or a nurse's observation of pain or adverse reaction to analgesic treatment in the Control group served as a "call-out alarm" for an anaesthesiologist. RESULTS: We found no significant differences in the mobility degree and number of postoperative nonsurgical complications between the groups. LOS was significantly shorter with 12.7 ± 6.3 days (mean ± SD) in the ESS group versus 14.2 ± 6.2 days in the Control group (P < 0.001). CONCLUSION: Postoperative ESS recording in combination with the possibility to call upon an anaesthesiologist when exceeding the threshold score might have contributed to the reductions of LOS in this two-centre study. This trial is registered with NCT02143128.

The Influence of Age on Interaction between Breath-Holding Test and Single-Breath Carbon Dioxide Test.

Introduction. The aim of the study was to compare the breath-holding test and single-breath carbon dioxide test in evaluation of the peripheral chemoreflex sensitivity to carbon dioxide in healthy subjects of different age. Methods. The study involved 47 healthy volunteers between ages of 25 and 85 years. All participants were divided into 4 groups according to age: 25 to 44 years (n = 14), 45 to 60 years (n = 13), 60 to 75 years (n = 12), and older than 75 years (n = 8). Breath-holding test was performed in the morning before breakfast. The single-breath carbon dioxide (SB-CO2) test was performed the following day. Results. No correlation was found between age and duration of breath-holding (r = 0.13) and between age and peripheral chemoreflex sensitivity to CO2 (r = 0.07). In all age groups there were no significant differences in the mean values from the breath-holding test and peripheral chemoreflex sensitivity tests. In all groups there was a strong significant inverse correlation between breath-holding test and SB-CO2 test. Conclusion. A breath-holding test reflects the sensitivity of the peripheral chemoreflex to carbon dioxide in healthy elderly humans. Increasing age alone does not alter the peripheral ventilatory response to hypercapnia.

Evaluation of Breath-Holding Test in Assessment of Peripheral Chemoreflex Sensitivity in Patients with Chronic Heart Failure.

BACKGROUND: The sensitivity of peripheral chemoreflex is a marker of the severity of heart failure and the prognosis of the outcome in these patients. The assessment of chemosensitivity in these patients remains an actual problem. OBJECTIVE: The aim of the study was to explore the relationship between a Breath-Holding Test (BHT) and single-breath carbon dioxide test and to evaluate the reliability of both tests in patients with Heart Failure (HF). METHOD: The study was performed in 43 patients with chronic heart failure. All subjects underwent BHT and single-breath carbon dioxide (CB-CO2), the evaluation of both tests was repeated a month later. Relationship of two test was evaluated by correlation analysis. Reliability was assessed with calculation of Standard Error of Measurement (SEM), Coefficient of Variation (CV) and Intraclass Correlation Coefficient (ICC). RESULTS: The duration of the breath-holding was inversely correlated to the result of CB-CO2 test (r = -0.86 at first measurement and r = -0.79 after a month) The ICC was 0.87 (95%CI: 0.78-0.93) for SB-CO2 test and 0,93 (95%CI: 0.88-0.96) for BHT, the CV was 24% for SB-CO2 and 13% for BHT. SEM for SB-CO2 test was 0.04 L / min / mmHg and limits of variation was 0.11 L / min / mmHg; SEM for BHT was 3.6 sec and limits of variation was10 sec. CONCLUSION: Breath-holding test is a reliable and safe method for assessing the sensitivity of peripheral chemoreflex to carbon dioxide in patients with heart failure.

Breath-holding test in evaluation of peripheral chemoreflex sensitivity in healthy subjects.

The aim of the study was to determine the feasibility of using a breath-holding test in assessing the sensitivity of the peripheral chemoreflex compared with the single-breath carbon dioxide test. The study involved 48 healthy volunteers between the ages of 18-29 years. The breath-holding test was performed followed by the single-breath carbon dioxide test on the next day. A month after the first tests, these tests were repeated to evaluate their reproducibility The coefficient of variability in the single-breath carbon dioxide test ranged from 0 to 32% with a mean of 10±7%. The mean coefficient of variability of the breath-holding test was 6±4% (0-19%). A significant inverse correlation between the results of the two tests was noted following analysis (r=-0.82, p<0.05). CONCLUSION: A breath-holding test after deep inspiration reflects the sensitivity of the peripheral chemoreflex as defined by the single-breath carbon dioxide test in healthy subjects.

Recruitment Maneuver in Elderly Patients with Different Peripheral Chemoreflex Sensitivity during Major Abdominal Surgery.

The goal of the study was to evaluate the effect of a recruitment maneuver on respiratory biomechanics, oxygenation, and hemodynamics in patients suffering from chronic heart failure with different peripheral chemoreflex sensitivity. The study was conducted in 115 elderly patients which underwent major abdominal surgery under general/epidural surgery. Peripheral chemoreflex sensitivity (PCS) was evaluated with breath-holding duration (BHD) during breath-holding test. All patients were divided into two groups: group H had a high PCS (BHD = 38 seconds or less, n = 49); Group M had a middle PCS (BHD more than 38 seconds, n = 66). Recruitment maneuver improved oxygenation and respiratory biomechanics in all cases. However, cardiac output decreased by an average of 18%-31% in group H compared to 18%-28% in group M. SVR either remained unchanged or decreased by up to 14% of the initial value in group H, while, in group M, it had a tendency to increase, which was 24% of the initial value. So, recruitment maneuver is an effective method to improve oxygenation and biomechanical properties of the respiratory system but in patients with increased peripheral chemoreflex sensitivity it associates with the risk of hemodynamic disturbances.

Safety and efficacy of combined epidural/general anesthesia during major abdominal surgery in patients with increased intracranial pressure: a cohort study.

BACKGROUND: The increased intracranial pressure can significantly complicate the perioperative period in major abdominal surgery, increasing the risk of complications, the length of recovery from the surgery, worsening the outcome. Epidural anesthesia has become a routine component of abdominal surgery, but its use in patients with increased intracranial pressure remains controversial. The goal of the study was to evaluate the safety and efficacy of epidural anesthesia, according to monitoring of intracranial pressure in patients with increased intracranial pressure. METHODS: The study includes 65 surgical patients who were routinely undergone the major abdominal surgery under combined epidural/general anesthesia. Depending on the initial ICP all patients were divided into 2 groups: 1 (N group) - patients with the normal intracranial pressure (≤12 mm Hg, n = 35) and 2 (E group) - patients with the elevated intracranial pressure (ICP > 12 mm Hg, n = 30). During the surgery we evaluated ICP, blood pressure, cerebral perfusion pressure (CPP). The parameters of recovery from anesthesia and the effectiveness of postoperative analgesia were also assessed. RESULTS: In N group ICP remained stable. In E group ICP decreased during anesthesia, the overall decline was 40% at the end of the operation (from 15 to 9 mm Hg (P <0.05)). The correction of MAP with vasopressors to maintain normal CPP was required mainly in patients with increased ICP (70% vs. 45%, p <0.05). CPP declined by 19% in N group. In E group the CPP reduction was 23%, and then it remained stable at 60 mm Hg. No significant differences in time of the recovery of consciousness, effectiveness of postoperative analgesia and complications between patients with initially normal levels of ICP and patients with ICH were noted. CONCLUSIONS: The combination of general and epidural anesthesia is safe and effective in patients with increased intracranial pressure undergoing elective abdominal surgery under the condition of maintaining the arterial pressure. Its use is not associated with the increase in intracranial pressure during the anesthesia, but it needs an intraoperative monitoring of ICP in order to prevent CPP reduction.