Treatment challenges in the management of difficult-to-treat gram-positive infections: A consensus view apropos therapeutic role of novel anti-MRSA antibiotics, levonadifloxacin (IV) and alalevonadifloxacin (oral).

PURPOSE: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities. METHOD: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached. RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia. CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.

India-discovered levonadifloxacin & alalevonadifloxacin: A review on susceptibility testing methods, CLSI quality control and breakpoints along with a brief account of their emerging therapeutic profile as a novel standard-of-care.

BACKGROUND: Levonadifloxacin (intravenous) and alalevonadifloxacin (oral prodrug) are novel antibiotics based on benzoquinolizine subclass of fluoroquinolone, licensed for clinical use in India in 2019. The active moiety, levonadifloxacin, is a broad-spectrum antibiotic with a high potency against methicillin-resistant Staphylococcus. aureus, multi-drug resistant pneumococci and anaerobes. OBJECTIVE: This review, for the first time, critically analyses the antimicrobial susceptibility testing methods, Clinical Laboratory & Standards Institute (CLSI)-quality control of susceptibility testing and breakpoints of levonadifloxacin. Further, the genesis, discovery and developmental aspects as well as therapeutic profile of levonadifloxacin and alalevonadifloxacin are briefly described. CONTENTS: In order to aid the scientific and clinician communities with a single comprehensive overview on all the key aspects of levonadifloxacin and alalevonadifloxacin, the present article covers the reference MIC and disk diffusion methods for levonadifloxacin susceptibility testing that were approved by CLSI and the reference ranges for quality control strains published in the CLSI M100 document. The breakpoints of levonadifloxacin were derived in concordance to US FDA, European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI approaches. Further, the article provides a brief account of challenges encountered during the discovery stages of levonadifloxacin and alalevonadifloxacin, activity spectrum and safety benefits accruing from structural novelty-linked mechanism of action. Further, the review also covers in vitro and in vivo activities, registrational clinical studies and patient-friendly features of levonadifloxacin/alalevonadifloxacin. Cumulatively, levonadifloxacin has a potential to offer a long awaited new standard-of-care treatment for the resistant Gram-positive bacterial infections.

Safety and efficacy of convalescent plasma as a therapy for SARS-CoV-2: A systematic review and meta-analysis.

Background and Aims: The safety and efficacy of convalescent plasma therapy (CPT) in SARS-CoV-2 is promising but intriguing due to heterogeneity of published studies. We conducted this systematic review and meta-analysis of convalescent plasma use in COVID-19 to identify its safety and efficacy. Material and Methods: We comprehensively searched the databases - PubMed, Web of Science, Embase, and the Cochrane Library for journal papers published between December 2019 and January 2021 about the use of CPT in SARS-CoV-2, and performed a meta-analysis using random effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Of 1529 records, 11 studies were eligible (five RCTs, two nonrandomized intervention trials, three prospective observational, and one retrospective), and all were conducted in confirmed patients of SARS-CoV-2. Out of the 11 studies, four investigated the effect of CPT on mortality, three on symptom alleviation, five on duration of hospital stay, four on time to discharge, three on the effect on viral clearance, three on the improvement in antibody titers, two on oxygen requirement, and two on adverse events. The pooled estimate for relative risk of death from SARS-CoV-2 was no different after CPT than control (RR: 0.87, 95% CI: 0.69, 1.10), (p = 0.426) but the relative risk of clinical improvement of symptoms was better after CPT (RR: 1.61, 95% CI: 0.97. 2.70). There was earlier hospital discharge after CPT over control (RR: 1.49, 95% CI: 0.79, 2.80), improved viral clearance (RR: 1.95; 95% CI: 1.07, 3.53), and quicker detection of antibody titer (RR: 1.95; 95% CI: 1.07, 3.53). No difference was observed for adverse effects between CPT and control (RR: 0.92.; 95% CI: 0.63 1.35). Conclusion: CPT appears to be a safe and promising treatment in moderate to severe SARS-CoV-2 leading to faster clinical improvement, reduced oxygen requirement, early hospital discharge, and quicker emergence of protective antibodies despite having no mortality benefit.

An Observational Study on the Effects of Delayed Initiation of End-of-Life Care in Terminally ill Young Adults in the Intensive Care Unit.

INTRODUCTION: The early initiation of end-of-life (EOL) care in terminally ill patients in the intensive care unit (ICU) offers distinct advantages but requires the consent and cooperation of the patients or their relatives. The terminally ill young adults pose distinct set of challenges. The present study was conducted to measure the prevalence and identify and compare the risk factors for the delayed initiation of EOL in terminally ill young adults. METHODS: The retrospective study was conducted in a mixed medical-surgical 7-bedded ICU after extracting the medical records of all terminally ill young adults in the age group of 20-40 years admitted between June 2014 and November 2018. Only "treatment futile" patients were eligible for inclusion. The patients already on EOL care or with unproven diagnosis were excluded from the study. The commencement of EOL care was divided into (a) normal group (N) and (b) late group (L). The two groups were compared with respect to the demographic factors, outcome, and patient satisfaction level. The factors responsible for the delay were investigated. All statistical analyses were performed using software SPSS 21.0 (SPSS, Inc., Chicago, IL, USA). RESULTS: Out of 66 terminally ill young adults with treatment futility, 23 (38.9%) were in the N group and 36 (61.1%) were in the L group (0.8 ± 0.4 days vs. 3.1 ± 1.6 days; P = 0.01). The education level and social and family support of the relatives of the N group were higher (P = 0.03; P - 0.04). The N group had lesser drug consumption of ICU resource usage (14.7% vs. 36.1%, P = 0.01; 18.5% vs. 24.7%, P = 0.04). There was no difference in the duration of mechanical ventilation, ICU stay, and satisfaction level at the time of discharge (or death) from the ICU. CONCLUSIONS: Our study found a high prevalence of delayed initiation of EOL care in terminally ill young adults and identified the factors responsible for them. The normal initiation of EOL care reduced the usage of medications and resources without affecting the level of patient satisfaction.

The efficacy and safety of hydroxychloroquine (HCQ) in treatment of COVID19 -a systematic review and meta-analysis.

INTRODUCTION: The treatment of SARS CoV2 (Severe Acute Respiratory Syndrome corona virus 2) also known as COVID-19 (corona virus disease 2019) continues to remain an enigma even after six months of the pandemic. Hydroxychloroquine (HCQ) has been one of the most widely tested drugs for SARS CoV2 on account of its antiviral properties. However the results so far have been far from categorical. The meta-analyses conducted till date are also lacking in precision and appropriateness. This systematic review and meta-analysis addresses the efficacy and safety of HCQ in SARS CoV2 by overcoming the limitations of earlier meta-analysis. METHODS: A total of 5 prominent medical databases were searched and fourteen studies (n = 12455) were included in the systematic review and meta-analyses. The data on survival, alleviation of symptoms, conversion of RT PCR positivity to negativity, use and efficacy in presence of co-morbidities (Hypertension, diabetes and heart disease) and cardiac and gastrointestinal side effects were extracted. Meta-analysis was applied to calculate the pooled estimates. Fixed-effects model results were chosen since I2 was <25%.Meta-analysis was conducted using STATA version 13 (StataCorp LP, College Station, TX, USA). RESULTS: The pooled estimates showed that HCQ treatment did not significantly affect survival at 14 and 28 days in COVID-19 patients with respect to the control population (RR: 1.003, 95% CI: 0.983-1.022), alleviation of symptoms at day 10 (RR: 1.044, 95% CI: 0.911 1.196), success in presence of co-morbidities (RR: 1.058, 95% CI: 1.035-1.082) and conversion from RT PCR positive to RT PCR negative on day 6 (RR:1.123, 95% CI: 1.041 1.212). There was higher risk for cardiac side effects (RR: 2.012, 95% CI: 1.428 2.833) and gastrointestinal side effects (RR: 1.318, 95% CI: 0.730 2.380) in HCQ recipients. CONCLUSION: There is no evidence on the safety and efficacy of HCQ either alone or in combination with other drugs in SARS CoV2 infection.

A Comparison of Acute Physiology and Chronic Health Evaluation II Score and Serum Procalcitonin Change for Predicting Mortality in Acute Pancreatitis.

INTRODUCTION: The prediction of mortality in acute pancreatitis (AP) is a useful estimate for effective treatment. Scoring systems such as acute physiology and chronic health evaluation (APACHE) II, computed tomography (CT) severity index (CTSI), bedside index of severity in acute pancreatitis (BISAP), etc., are used for prediction. Biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) are also considered useful for prognostication. The aim of this retrospective study was to correlate the changes in serum PCT level with APACHE II score between admission and 48 hours as mortality predictor in AP. MATERIALS AND METHODS: The observational study was conducted in a cohort of 42 patients admitted consecutively in the seven-bedded general intensive care unit (ICU) of our institute between June 2016 and May 2018, with the diagnosis of AP. The APACHE II score and serum PCT level at admission and 48 hours were retrieved from the hospital database. The change in APACHE II and PCT level was compared between ICU "survivors" and "nonsurvivors." The predictive accuracy of APACHE II and PCT was measured using area under receiver-operator characteristics (ROC) curve. A p value <0.05 was considered as significant. RESULTS: Of the 42 patients enrolled, 30 patients (71.42%) were survivors and 12 (28.58%) were nonsurvivors. The median APACHE II score in nonsurvivors increased from 16 (7-19) to 23 (11-29) and remained unchanged at 16 (9-19 at admission; 10-22 at 48 hours) in survivors. The median PCT levels increased from 3.8 (1.2-5.6) to 6.2 (1.9-12.5) in nonsurvivors and decreased from 3.8 (1.2-5.6) to 2.2 (0.6-2.9) in survivors. Serum PCT change compared better than the APACHE II score change among survivors (r = 0.455, p = 0.011) with a mean (±standard deviation SD) change of 1.41 (±1.59). CONCLUSION: The change in serum PCT and APACHE II between admission and 48 hours correlates well and is useful for mortality prediction in AP. Serum PCT change compares better than APACHE II score change in survivors. HOW TO CITE THIS ARTICLE: Choudhuri AH, Duggal S, Biswas PS, Uppal R. A Comparison of Acute Physiology and Chronic Health Evaluation II Score and Serum Procalcitonin Change for Predicting Mortality in Acute Pancreatitis. Indian J Crit Care Med 2020;24(3):190-194.

A survey of physicians' appreciation and knowledge about airway safety measures in the wake of COVID-19 pandemic.

BACKGROUND AND AIMS: The implementation of safety measures during airway management is a major concern to prevent COVID-19 transmission during pandemic. Various guidelines and advisories are in vogue to ensure safe practices. However, their success depends on the caregivers' knowledge and understanding. This survey was conducted to assess the knowledge and safety concerns amongst physicians towards airway management in the background of COVID-19 pandemic. MATERIAL AND METHODS: A survey instrument of thirty questions covering three timelines of airway management viz. 'before', 'during' and 'after' airway intervention was created. The questionnaire was electronically mailed to the eligible physicians over a period of one month via a web-based platform and the responses were analyzed. The responses were depicted numerically as percentage. A multiple discriminant analysis was used to test the accuracy of responses after adjusting for common variables. RESULTS: Out of 407 responses, 300 were eligible for analysis. The respondents with correct answers to questions with single correct response were 46%, 69% and 57.3%, along the three timelines and the respondents with more than 75% correct responses in questions with multiple correct responses were 49%, 58% and 31% along the same timelines. About 75% of the participants became aware of transmission through aerosols aftermath pandemic. About two-third of the participants had knowledge about the safety guidelines and recommendations. Majority of the respondents were aware of the safety measures 'during airway intervention'. CONCLUSION: Our study found satisfactory knowledge and appreciable concern among the practicing physicians regarding airway safety measures in the wake of COVID-19 pandemic. However, more physicians were aware about the measures required to be adopted 'during' airway intervention. The survey highlights the need for a more focused training of the caregivers about safety measures 'before' and 'after' airway intervention.

Epidemiology and risk factors for multidrug-resistant bacteria in critically ill patients with liver disease.

BACKGROUND AND AIMS: The critically ill patients with liver disease are vulnerable to infections in both community and hospital settings. The nosocomial infections are often caused by multidrug-resistant (MDR) bacteria. The present observational study was conducted to describe the epidemiology, course, and outcome of MDR bacterial infection and identify the risk factors of such infection in critically ill patients with liver disease. MATERIALS AND METHODS: A retrospective observational study was conducted on 106 consecutive critically patients with liver disease admitted in the Intensive Care Unit between March 2015 and February 2017. The MDR and non-MDR (non-MDR) groups were compared and the risk factors identified by multivariate analysis. RESULTS: Out of the 106 patients enrolled in the study, 23 patients had infections caused by MDR bacteria. The MDR-infected patients had severe liver disease (Child-Pugh score 11 ± 2.3 vs. 7 ± 3.9; P = 0.04), longer duration of antibiotic usage (6 ± 2.7 days vs. 2 ± 1.5 days; P = 0.04), greater use of total parenteral nutrition (TPN) (73.9% vs. 62.6%; P = 0.04), and more concurrent antifungal administration (60.8% vs. 38.5%; P = 0.04). The mortality was higher in MDR group (hazard ratio = 1.86; P < 0.05). The independent predictors of MDR bacterial infection were Child-Pugh score >10, prior carbapenem use, antibiotic use for more than 10 days, TPN use, and concurrent antifungal administration. CONCLUSION: The study demonstrated a high prevalence of MDR bacterial infection in critically ill patients with a higher mortality over non-MDR bacterial infection and also identified the independent predictors of such infections.

Epidemiology and characteristics of nosocomial infections in critically ill patients in a tertiary care Intensive Care Unit of Northern India.

BACKGROUND AND AIMS: The prevalence of nosocomial infection is higher in the Intensive Care Unit (ICU) than other areas of the hospital. The present observational study was undertaken to describe the epidemiology and characteristics of nosocomial infections acquired in a tertiary care ICU and the impact of the various risk factors in their causation. MATERIALS AND METHODS: A retrospective study was conducted on the prospectively collected data of 153 consecutive patients admitted in a tertiary care ICU between July 2014 and December 2015. The primary objective was to assess the epidemiology of ICU-acquired bacterial infections in terms of the incidence of new infections, causative organism, and site. The secondary end point was to assess the risk factors for developing ICU-acquired infections. RESULTS: Out of the 153 patients enrolled in the study, 87 had an ICU-acquired nosocomial infection (58.86%). The most common organism responsible for infection was Klebsiella pneumoniae (37%), and the most common infection was pneumonia (33%). The duration of mechanical ventilation and length of ICU stay were significantly prolonged in patients developing nosocomial infections. There was no difference in mortality between the groups. The multivariate analyses identified intubation longer than 7 days, urinary catheterization >7 days, duration of mechanical ventilation more than 7 days, and ICU length of stay longer than 7 days as independent risk factors for nosocomial infections. CONCLUSION: The study demonstrated a high incidence of nosocomial infection in the ICU and identified the risk factors for acquisition of nosocomial infections in the ICU.

Influence of Admission Source on the Outcome of Patients in an Intensive Care Unit.

AIM OF THE STUDY: The admission in the Intensive Care Unit (ICU) occurs from various sources, and the outcome depends on a complex interplay of various factors. This observational study was undertaken to describe the epidemiology and compare the differences among patients admitted in a tertiary care ICU directly from the emergency room, wards, and ICUs of other hospitals. MATERIALS AND METHODS: A retrospective study was conducted on 153 consecutive patients admitted from various sources in a tertiary care ICU between July 2014 and December 2015. The primary endpoint of the study was the influence of the admission source on ICU mortality. The secondary endpoints were the comparison of the duration of mechanical ventilation, length of ICU stay, and the ICU complication rates between the groups. RESULTS: Out of the 153 patients enrolled, the mortality of patients admitted from the ICUs of other hospital were significantly higher than the patients admitted directly from the emergency room or wards/operating rooms (60.5% vs. 48.2% vs. 31.9%; P = 0.02). The incidence of ventilator-associated lung injury was lower in the patients admitted directly from the emergency room (23.4% vs. 50% vs. 50%; P = 0.03). Multivariate logistic regression analysis revealed higher age, increased disease severity, longer duration of mechanical ventilation, and longer ICU stay as independent predictors of mortality in the patients shifted from the ICUs of other hospitals. CONCLUSION: The study demonstrated a higher risk of ICU mortality among patients shifted from the ICUs of other hospitals and identified the independent predictors of mortality.

Predictors of postoperative pulmonary complications after liver resection: Results from a tertiary care intensive care unit.

BACKGROUND: Postoperative pulmonary complication (PPC) is a serious complication after liver surgery and is a major cause of mortality and morbidity in the intensive care unit (ICU). Therefore, the early identification of risk factors of PPCs may help to reduce the adverse outcomes. OBJECTIVE: The aim of this retrospective study was to determine the predictors of PPCs in patients undergoing hepatic resection. DESIGN: Retrospective, observational. METHODS: The patients admitted after hepatic resection in the gastrosurgical ICU of our institute between October 2009 and June 2013 was identified. The ICU charts were retrieved from the database to identify patients who developed PPCs. A comparison of risk factors was made between the patients who developed PPC (PPC group) against the patients who did not (no-PPC group). RESULTS: Of 117 patients with hepatic resection, 28 patients developed PPCs. Among these, pneumonia accounted for 12 (42.8%) followed by atelectasis in 8 (28.5%) and pleural effusion in 3 (10.7%). Among the patients developing PPCs, 16 patients were over a 70-year-old (57.1%), 21 patients were smokers (75%) and 8 patients (28.5%) had chronic obstructive pulmonary disease (COPD). The requirement for blood transfusion and duration of mechanical ventilation were greater in the patients developing PPC (2000 ± 340 vs. 1000 ± 210 ml; 10 ± 4.5 vs. 3 ± 1.3 days). CONCLUSION: Old age, chronic smoking, COPD, increased blood product transfusion, increased duration of mechanical ventilation and increased length of ICU stay increased the relative risk of PPC, presence of diabetes and occurrence of surgical complications (leak, dehiscence, etc.) were independent predictive variables for the development of PPC.

Predictors of septic shock following anastomotic leak after major gastrointestinal surgery: An audit from a tertiary care institute.

BACKGROUND: Anastomotic leak is a serious complication after major gastrointestinal surgery and majority of deaths occur due to septic shock. Therefore, the early identification of risk factors of septic shock may help reduce the adverse outcomes. OBJECTIVE: The aim of this audit was to determine the predictors of septic shock in patients with anastomotic leak after major gastrointestinal surgery. DESIGN: Retrospective, audit. MATERIALS AND METHODS: The patients admitted in the gastrosurgical intensive care unit ICU) of our institute between September 2009 and April 2012 with anastomotic leakage after surgery were identified. The ICU charts were retrieved from the database to identify the patients progressing to septic shock. A comparison of risk factors was made between the patients who developed septic shock (septic shock group) against the patients who did not (non-septic shock group). RESULTS: The study sample comprised of 103 patients with anastomotic leak, of which 72 patients developed septic shock. The septic shock group had a higher APACHE II score, lower MAP, and higher HR at the time of ICU admission. They received greater transfusion of packed red blood cells during their ICU stay. Septic shock was more common after pancreaticojejunostomy and hepaticojejunostomy leaks. CONCLUSION: Presence of malignancy, chronic obstructive pulmonary disease (COPD), packed red blood cell transfusion, bacteremia, and hepaticojejunostomy or pancreaticojejunostomy leaks were independent predictors of mortality and length of ICU stay. To the best of our knowledge there are no available studies in the literature on the predictors of risk factors of septic shock in patients with anastomotic leakage.

Influence of non-surgical risk factors on anastomotic leakage after major gastrointestinal surgery: Audit from a tertiary care teaching institute.

CONTEXT: The occurence of anastomotic leakage after gastointestinal resection and anastomosis is associated with significant mortality and morbidity. AIMS: There is dearth of evidence in the literature on the influence of various non-surgical factors in causing anastomotic leakage although many studies have identified their possible role. MATERIALS AND METHODS: A retrospective audit of all the anastomotic leakages occurring between September 2009 and April 2012 in our institute was performed to identify the potential non-surgical factors that can influence anastomotic leakage. A total of 137 out of 1246 patients who developed anastmotic leak were analyzed. All the potential non-surgical causes of anastomotic leakage available in the literature were analyzed by univariate analysis and stepwise multiple logistic regression analysis was done after adjusting for the type of surgery. An intergroup comparison among the patients based on the type of surgery was also performed. RESULTS: THE FOLLOWING FACTORS WERE FOUND TO BE INDEPENDENTLY ASSOCIATED WITH INCREASED RISK OF ANASTOMOTIC LEAK: (1) albumin <3.5 g/dl, (2) anemia <8 g/dl, (3) hypotension (4) use of inotropes, and (5) blood transfusion. The majority of anastomotic leaks occurred after pancreatic surgeries followed by esophagectomies and occurred least after colonic resections. The risk for anastomotic leak was four times more in patients who required inotropic support in the perioperative period and three times more in patients who developed hypotension. CONCLUSIONS: Our study is the first retrospective audit to identify the influence of non-surgical factors for anastomotic leakage and the need for further observational studies in this direction.

Palliative care for patients with chronic obstructive pulmonary disease: current perspectives.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory illness with a myriad of disabling symptoms and a decline in the functional parameters that affect the quality of life. The mortality and morbidity associated with severe COPD is high and the patients are mostly housebound and in need of continuous care and support. The uncertain nature of its prognosis makes the commencement of palliative care and discussion of end-of-life issues difficult even in the advanced stage of the disease. This is often compounded by inadequate communication and counseling with patients and their relatives. The areas that may improve the quality of care include the management of dyspnea, oxygen therapy, nutritional support, antianxiety, and antidepressant treatment, and advance care planning. Hence, it is necessary to pursue a holistic care approach for palliative care services along with disease-specific medical management in all such patients to improve the quality of life in end-stage COPD.

A comparison between intravenous paracetamol plus fentanyl and intravenous fentanyl alone for postoperative analgesia during laparoscopic cholecystectomy.

PURPOSE: our study compared the effect of fentanyl alone with fentanyl plus intravenous Paracetamol for analgesic efficacy, opioid sparing effects, and opioid-related side effects after laparoscopic cholecystectomy. MATERIALS AND METHODS: eighty patients undergoing laparoscopic cholecystectomy were randomized into two groups, who were given either an IV placebo or an IV injection of 1g paracetamol just before induction. Both groups received fentanyl during induction and IM diclofenac for pain relief every 8 hourly for 24 h after surgery. The postoperative pain relief was evaluated by a visual analog scale (VAS) and consumption of fentanyl as rescue analgesic in the postoperative period for 24 h after surgery was measured. The incidence of PONV and sedation scores was also measured in the postoperative period. RESULTS: the mean VAS score in first and second hour after surgery was less in the group receiving IV Paracetamol (3.3±0.4* vs. 5.2±0.9; 3.1±0.4* vs. 4.3±0.3); the fentanyl consumption over first 24 h was also less in the group receiving IV paracetamol (50±14.9 vs. 150±25.8). The time requirement of first dose of rescue analgesic in the postoperative period was also significantly prolonged in the group receiving IV paracetamol (76±24.7 vs. 48±15.8). There was no difference in the sedation scores and in the incidence of PONV in the two groups. CONCLUSION: The study demonstrates the usefulness of intravenous paracetamol as pre-emptive analgesic in the treatment of postoperative pain after laparoscopic cholecystectomy.