Identifying critically ill patients with cirrhosis who benefit from nutrition therapy: the mNUTRIC score study.

Background and Aim: Malnutrition increases risk of mortality in critically ill patients with cirrhosis. Modified Nutrition Risk in Critically ill (mNUTRIC) score is a validated tool to identify at risk patients who may benefit from goal-directed nutrition therapy. We aimed to study the association between mNUTRIC score and 28-day mortality in critically ill patients with cirrhosis. Methods: A prospective study was conducted in the liver intensive care unit of a quaternary teaching institute. Baseline and follow-up data pertaining to mNUTRIC score, clinical, hemodynamic, biochemical, nutritional parameters, mechanical ventilation, length of ICU stay, and development of sepsis were collected. Correlation between mNUTRIC score and its modulation by nutritional adequacy was determined. Results: One hundred and fifty patients were enrolled. Out of these, 116 (77%) had a high NUTRIC score (HNS) and 34 (23%) had a low NUTRIC score (LNS). Patients with HNS had higher mortality (54% vs. 10%; P = 0.008), longer mechanical ventilation (P = 0.02), and high incidence of sepsis (32% vs. 2.6%; P = 0.002) compared to LNS. The probability of survival increased with increase in nutritional adequacy (P < 0.01) in patients with HNS. Conclusion: mNUTRIC score is a useful tool for identifying nutrition risk in critically ill patients with cirrhosis. Goal-directed nutrition therapy in patients with HNS can significantly improve survival. Relevance for Patients: Critically ill patients with cirrhosis who are at a higher nutritional risk as identified by the mNUTRIC score may have a better survival benefit if higher calorie and protein adequacy are achieved in the ICU.

Sarcopenia is the independent predictor of mortality in critically ill patients with cirrhosis.

Background: Sarcopenia is strongly associated with poor outcome in cirrhosis. There are little prospective data that sarcopenia influences outcomes in critically ill cirrhotics (CICs). Computed tomography (CT) is the gold standard for sarcopenia assessment in the intensive care unit (ICU), as it is independent of hydration status. Aim: This study aims to assess the prevalence of sarcopenia and study its impact on clinical outcomes in CICs. Methods: In this prospective observational study, CICs admitted to the liver ICU were enrolled, if meeting inclusion (age 18-70 years, abdominal CT scan within three months before ICU admission) and exclusion criteria (survival likely to be <24 h, coexisting chronic diseases). Clinical, hemodynamic, biochemical, and nutritional parameters, including length of stay (LOS), duration of mechanical ventilation (MV), development of new-onset infections (NOI), incidence of new-onset acute kidney injury (AKI), and overall survival, were recorded. CT images at the L3 level were analyzed using Slice-O-Matic V4.3 software to assess the skeletal muscle index (SMI) expressed as skeletal muscle area (cm2)/height (m2). Sarcopenia was defined if SMI was <50 cm2/m2 - males and <39 cm2/m2 - females. Data were analyzed using SPSS version 22. Results: Altogether 111 patients (M-83.8%; age 48.4±11.3 years; etiology: Alcohol - 56 [50.5%], non-alcoholic steatohepatitis - 27 [24.3%], viral - 12 [10.8%], and others - 16 [14.4%]; Child-Turcotte-Pugh - 11.9±1.8; model for end-stage liver disease - 27.8±7.3; sequential organ failure assessment - 10.5±4.1; APACHE - 23±8; and MV - 54 [48.6%]) were enrolled. Of these, 76 (68.5%) were sarcopenic and 35 (31.5%) non-sarcopenic. Sarcopenic CICs had higher overall mortality (72.4%) compared to non-sarcopenics (40%) (P=0.001, OR [95% CI] - 3.93 [1.69-9.12]), and higher prevalence of sepsis at ICU admission (53.9% vs. 31.4%, P=0.027, OR [95% CI] - 1.7 [1.0-2.92]) than non-sarcopenics. LOS, duration of MV, incidence of NOI, and development of new-onset AKI were comparable between groups. Multivariate binary logistic regression showed that sarcopenia, sepsis, and APACHE II score were independently associated with mortality. Conclusion: Two-thirds of CICs have sarcopenia at ICU admission, making them 1.7 times more susceptible to sepsis and increasing the risk of mortality by almost 4-fold in the ICU. Relevance for Patients: Almost 70% of patients with chronic liver disease admitted to the ICU have low muscle mass (sarcopenia). The presence of sarcopenia per se makes them highly prone to infections and increases the chances of death by almost 4-fold; thus, highlighting the importance of nutrition optimization in this patient group.

Evaluation of the Integrative Weaning Index for Predicting the Outcome of Spontaneous Breathing Trial in Patients with Cirrhosis on Mechanical Ventilation: A Pilot Study.

OBJECTIVE: Studies on mechanical ventilation in patients with cirrhosis have focused mainly on survival, as the disease is considered to carry a poor prognosis. The process of weaning in these patients has never been studied. With improving survival, it would be ideal to study the weaning indices that could add experience in clinical management. The integrative weaning index is known to predict weaning failure, even in those who tolerate the spontaneous breathing trial. However, it has been evaluated mainly in patients with chronic obstructive pulmonary disease. Our aim is to study the integrative weaning index in predicting the outcome of the spontaneous breathing trial in patients with cirrhosis undergoing mechanical ventilation. METHODS: Adult cirrhotic patients requiring mechanical ventilation for the first time were enrolled. Twenty-seven patients were found eligible for weaning. After the decision to wean, the patients were put on pressure support mode of ventilator followed by spontaneous breathing trial using T-piece for 2 hours. RESULTS: The study population was divided into two groups: successful spontaneous breathing trial group (Group S) and unsuccessful spontaneous breathing trial group (Group U) based on the outcome of the breathing trial. The mean respiratory rate was significantly lower in Group S as compared to Group U. The compliance of the respiratory system and integrative weaning index were found to be significantly higher in Group S. An integrative weaning index of 28 mL/cmH2O breaths/min/L was found to be a good predictor of weaning success. CONCLUSIONS: Our results demonstrate that weaning from mechanical ventilation is possible in critically ill patients with cirrhosis. An integrative weaning index of 28 mL/cmH2O breaths/min/L could be a successful predictor of weaning from mechanical ventilation.

Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial).

IMPORTANCE: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. OBJECTIVE: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. DESIGN, SETTING AND PARTICIPANTS: A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. INTERVENTION: One group received COPLA with SMT (n=200), and another group received SMT only (n=200). MAIN OUTCOME MEASURES: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. RESULTS: The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. CONCLUSION AND RELEVANCE: Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. TRIAL REGISTRATION NUMBER: NCT04425915.

EEG abnormality as a prognostic factor in cirrhotic patients with Grade III-IV hepatic encephalopathy requiring mechanical ventilation: A retrospective analysis.

BACKGROUND AND AIM: Hepatic encephalopathy is a serious complication that entails liver cirrhosis with a high mortality rate. The Child- Turcotte-Pugh class (CTP class) and model for end-stage liver disease (MELD) score are two important prognostic indicators for cirrhosis, while sequential organ failure assessment (SOFA) is a dynamic score for the assessment of critically ill patients. Patients with liver disease with advanced CTP class and higher MELD scores have poor prognosis. The aim of this study was to evaluate the role of electroencephalography (EEG) in cirrhotic patients requiring ventilator support for hepatic encephalopathy Grade III-IV. METHODS: A retrospective study was conducted on patients admitted to the liver intensive care unit (ICU) of a tertiary teaching institute. EEG records of 92 patients with Grade III-IV hepatic encephalopathy who were admitted between April 2015 and May 2017 to the liver ICU were analyzed. The correlation between EEG findings and 28-day mortality, ICU length of stay, and the number of days on mechanical ventilation was determined. RESULTS: Seventy-eight of 92 patients (85%) exhibited bilateral slowing EEG pattern, suggestive of encephalopathy. A triphasic pattern was the most common EEG abnormality in 40% (31 of 78) of the patients. Patients with abnormal EEG had a significantly higher MELD score compared to those with a normal EEG (P=0.02). There were no significant differences in length of mechanical ventilation between both groups, but an increasing trend was observed in those with abnormal EEG (P=0.09). CONCLUSION: EEG findings correlate well with severity of disease in critically ill patients with liver disease. RELEVANCE FOR PATIENTS: EEG has a role in monitoring and prognostication of hepatic encephalopathy in critically ill patients with liver disease.

Efficacy and safety of an open lung ventilation strategy with staircase recruitment followed by comparison on two different modes of ventilation, in moderate ARDS in cirrhosis: A pilot randomized trial.

Background: Mechanical ventilation in cirrhosis with acute respiratory distress syndrome (ARDS) is not widely studied. We aimed to study the effect of the staircase recruitment manoeuvre followed by two different modes of ventilation. Methods: Thirty patients with cirrhosis with moderate ARDS underwent the staircase recruitment manoeuvre followed by randomisation to volume control or pressure control group. Results: The PaO2/FiO2 ratio showed a significant improvement in both the groups after recruitment. The improvement was significantly higher in the pressure control ventilation (PCV) group at the end of the first hour as compared to the volume control ventilation (VCV) group. However, this difference was not significant at the end of 6 and 12 h. In the PCV group it improved from 118.47 ± 10.21 at baseline to 189.87 ± 55.18 12 h post-recruitment. In the VCV group it improved from 113.79 ± 13.22 at baseline to 180.93 ± 81.971. Static lung compliance also improved in both the groups significantly (P < 0.001). The PCV group showed an improvement from 25.42 ± 11.94 mL/cm H2O at baseline to 29.51 ± 14.58 mL/cm H2O. In the VCV group the lung compliance improved from 24.78 ± 4.87 mL/cm H2O to 31.31 ± 10.88 mL/cm H2O. Conclusion: This study shows that stepwise recruitment manoeuvre is an effective rescue therapy to improve oxygenation in cirrhosis with moderate ARDS. PCV may have an advantage over VCV in terms of better oxygenation.

Open Abdomen in a Critically Ill Patient.

One of the damage control strategies used to avoid or treat abdominal compartment syndrome is "open abdomen (OA)," where the facial edges and the skin is left open, exposing the abdominal viscera. Although it reduces the mortality both in trauma and non-trauma abdominal complications, it does create a significant challenge in an intensive care setting, as it has physiological consequences that need early recognition and prompt treatment both in the intensive care unit and in the operating room. The article aims to review literature on "open abdomen," describe the challenges in such cases, and proposes a guideline for the intensivist in managing a patient with an OA. How to cite this article: Mitra LG, Saluja V, Dhingra U. Open Abdomen in a Critically Ill Patient. Indian J Crit Care Med 2020;24(Suppl 4):S193-S200.

Tracheostomy in critically ill liver disease patients with coagulopathy: A retrospective study at a tertiary center.

INTRODUCTION: Critically ill patients with liver disease commonly present to the intensive care unit (ICU) with need for prolonged ventilation, difficult weaning, and refractory coagulopathy. These patients experience both bleeding and thrombotic complications with a precariously balanced state of coagulopathy. The purpose of this study was to assess the bleeding complications of tracheostomy in critically ill patients with liver disease. METHODS: A retrospective study was conducted in liver ICU of a tertiary teaching institute. Medical records were analyzed to assess postprocedure complication rate among 73 critically ill liver disease patients who had undergone tracheostomy during the period of October 2017 to September 2018. RESULTS: Ten out of 73 patients (13%) required transfusion of blood products after 12 h of procedure, despite thromboelastography (TEG)-based correction prior to procedure. Of these, 7 patients (9%) underwent surgical tracheostomy (ST) and three patients (4%) underwent percutaneous tracheostomy. Statistically no significant difference in bleeding was seen among the two groups, but a rising trend was seen with the ST group (P = 0.52). None of the patients experienced procedure-related pneumothorax and subcutaneous emphysema, as observed in the chest X-ray. CONCLUSION: We conclude that coagulopathy should not be deterrence for the performance of tracheostomy in critically ill patients with liver disease. Adequate clotting support guided by the global tests of coagulation, such as TEG, ensures lesser incidence of bleeding.

Thromboelastography-Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial.

Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (international normalized ratio [INR] and platelet [PLT] count), and its use may avoid unnecessary blood component transfusion in patients with advanced cirrhosis and significant coagulopathy who have nonvariceal upper gastrointestinal (GI) bleeding. A total of 96 patients with significant coagulopathy (defined in this study as INR >1.8 and/or PLT count < 50 × 109 /L) and nonvariceal upper GI bleed (diagnosed after doing upper gastrointestinal endoscopy, which showed ongoing bleed from a nonvariceal source) were randomly allocated to TEG-guided transfusion strategy (TEG group; n = 49) or standard-of-care (SOC) group (n = 47). In the TEG group, only 26.5% patients were transfused with all three blood components (fresh frozen plasma [FFP], PLTs, and cryoprecipitate) versus 87.2% in the SOC group (P < 0.001). Although 7 (14.3%) patients in the TEG group received no blood component transfusion, there were no such patients in the SOC group (P = 0.012). Also, there was a significantly lower use of blood components (FFP, PLTs, and cryoprecipitate) in the TEG group compared with the SOC group. Failure to control bleed, failure to prevent rebleeds, and mortality between the two groups were similar. Conclusion: In patients with advanced cirrhosis with coagulopathy and nonvariceal upper GI bleeding, TEG-guided transfusion strategy leads to a significantly lower use of blood components compared with SOC (transfusion guided by INR and PLT count), without an increase in failure to control bleed, failure to prevent rebleed, and mortality.

Treatment with carvedilol improves survival of patients with acute-on-chronic liver failure: a randomized controlled trial.

BACKGROUND AND AIMS: In addition to the portal pressure reducing effect, non-selective beta blockers (NSBBs) have possible immunomodulatory and effect in reducing bacterial translocation. Recently, it has been shown that patients who are already on NSBBs should be continued on them (if feasible), if acute-on-chronic liver failure (ACLF) develops. It, however, remains unknown if patients with ACLF and no or small esophageal varices at presentation will benefit from the use of NSBBs. We studied the efficacy and safety of carvedilol in patients with ACLF in reducing mortality, variceal bleeding and non-bleeding complications. METHODS: 136 patients with ACLF (with no or small esophageal varices and HVPG ≥ 12 mmHg) were randomized to either carvedilol (n = 66) or placebo arms (n = 70). RESULTS: Within 28 days, 7 (10.6%) of 66 patients in the carvedilol group and 17 (24.3%) of 70 in the placebo group died (p= 0.044). Fewer patients in the carvedilol compared to placebo group developed acute kidney injury (AKI) (13.6% vs 35.7%, p = 0.003 and spontaneous bacterial peritonitis (SBP) (6.1% vs 21.4%, p= 0.013). Significantly, more patients in the placebo group had increase in APASL ACLF Research Consortium-ACLF grade (22.9% vs 6.1%, p= 0.007). There was no significant difference in the 90-day transplant-free survival rate and development of AKI, SBP, non-SBP infections (including pneumonia) and variceal bleed within 90 days, between the two groups. CONCLUSIONS: In ACLF patients with either no or small esophageal varices and HVPG ≥ 12 mmHg, carvedilol leads to improved survival and fewer AKI and SBP events up to 28 days. CLINICALTRIALS. GOV IDENTIFIER NUMBER: NCT02583698.

Comparison of Prognostic Models in Acute Liver Failure: Decision is to be Dynamic.

BACKGROUND AND AIMS: Acute liver failure (ALF) is a rare disease entity with a high mortality. Management is dependent on accurate prognostication. MATERIALS AND METHODS: One hundred consecutive patients presenting with ALF were prospectively evaluated. The King's college criteria (KCC), ALF early dynamic model (ALFED), sequential organ failure assessment (SOFA) score, and acute physiology and health evaluation II (APACHE II) scores were compared to predict mortality. RESULTS: There were significant differences in means of all the scores between survivors and nonsurvivors. The SOFA 48 hours had the highest area under receiver operating characteristic curve (AUC) (0.857) closely followed by the ALFED score (0.844). The optimal cutoff for the SOFA score at 48 hours to predict subsequent survival outcome is ≥10 and for the ALFED score is ≥5. Sequential organ failure assessment 48 hours had a good sensitivity of 87%, and the ALFED score showed a good specificity of 84%. The decision curve analysis showed that between a threshold probability of 0.13 and 0.6, use of the SOFA score provided the maximum net benefit and at threshold probabilities of >0.6, the use of ALFED score provided the maximum clinical benefit. CONCLUSION: Dynamic scoring results in better prognostication in ALF. The SOFA 48 hours and ALFED score have good prognostication value in nonacetaminophen-induced liver failure. HOW TO CITE THIS ARTICLE: Saluja V, Sharma A, Pasupuleti SSR, Mitra LG, Kumar G, Agarwal PM. Comparison of Prognostic Models in Acute Liver Failure: Decision is to be Dynamic. Indian J Crit Care Med 2019;23(12):574-581.

K time & maximum amplitude of thromboelastogram predict post-central venous cannulation bleeding in patients with cirrhosis: A pilot study.

BACKGROUND & OBJECTIVES: Coagulation and haemostasis are dynamic processes. The haemostatic changes in liver disease affect all aspects of coagulation. The prothrombin time (PT)/ international normalized ratio (INR) was developed to monitor oral anticoagulant therapy and the activated partial thromboplastin time to investigate inheritable single factor deficiencies. Viscoelastic tests such as thromboelastogram (TEG) give information about dynamics of clot formation (coagulation factor and anticoagulant activity), clot strength (platelets and fibrinogen) and clot stability (finbrinolysis and factor XIII). Administration of blood products before invasive procedures is still guided by INR and platelet count in patients of liver disease. This study was aimed to evaluate the validity of TEG to predict post-procedural bleed after central venous cannulation in patients with cirrhosis. METHODS: Ninety patients aged 20-70 yr diagnosed with liver cirrhosis requiring elective central venous catheter (CVC) insertion were studied. Platelet count, INR, serum creatinine, TEG and Child-Turcotte-Pugh (CTP) score were recorded before the procedure. Right-sided internal jugular vein was cannulated. On the basis of presence or absence of post-procedural bleed, patients were divided into bleeding and non-bleeding groups. The CTP score, component of TEG (R - reaction time, K - coagulation time, MA - maximum amplitude and α - angle) and laboratory parameters of both the groups were compared. RESULTS: Bleeding was seen more when CTP scores were ≥10 (P=0.05). The K time of 3.05 min or more on thromboelastograph was a significant predictor of bleeding [area under the curve (AUC) 0.694, P=0.047]. MA of 48.8 mm or more was a significant predictor of non-bleeding. INR ≥2.6 was a significant predictor of bleeding (AUC 0.765, P=0.005). K time had a low-positive predictive value of 20 per cent and the positive and negative likelihood ratios of 1.87 and 0.48, respectively. INTERPRETATION & CONCLUSIONS: Our results show that the cut-off value for INR ≥2.6 and K time ≥3.05 min predict bleeding and MA ≥48.8 mm predicts non-bleeding in patients with cirrhosis undergoing central venous pressure catheter cannulation.

Post-operative hypertension, a surrogate marker of the graft function and predictor of survival in living donor liver transplant recipients: A retrospective study.

BACKGROUND AND AIMS: De novo hypertension (HTN) in liver transplantation recipients is a known entity. We investigated haemodynamic behaviour after a liver transplant to see if it can predict survival to discharge from the hospital. METHODS: electronic records of Haemodynamic parameters and laboratory investigations of 95 patients of living donor liver transplant (LDLT) were retrospectively analysed. RESULTS: Twenty-three patients were operated for acute liver failure (ALF) and 72 patients for chronic liver disease (CLD). Eight patients of CLD and four of ALF did not survive. CLD patients had statistically significant rise in systolic blood pressure from the post-operative day (POD) 1 to POD 4 and diastolic blood pressure (DBP) from POD 3 to POD 6. Heart rate (HR) significantly decreased from POD 3 to POD 5. Haemodynamic parameters returned to baseline values within 20 days. Diastolic HTN had a positive predictive value of 100% for survival with 100% sensitivity and specificity. Systolic HTN had a positive predictive value of 100% for survival (sensitivity-89%, specificity-100%). ALF patients had a significant decrease in HR from POD 2 to POD 10. Bradycardia (HR ≤60/min) had a positive predictive value of 100% for survival with a sensitivity of 45% and 58% in CLD and ALF, respectively, with a specificity of 100% in both the groups. Non-survivors had no significant change in haemodynamics. In CLD group, International Normalised Ratio had statistically significant, strong negative correlation with DBP. CONCLUSION: Haemodynamic pattern of recovery may be used for predicting survival to discharge after LDLT.

Validation of a New "Objective Pain Score" Vs. "Numeric Rating Scale" For the Evaluation of Acute Pain: A Comparative Study.

BACKGROUND: Pain scores are used for acute pain management. The assessment of pain by the patient as well as the caregiver can be influenced by a variety of factors. The numeric rating scale (NRS) is widely used due to its easy application. The NRS requires abstract thinking by a patient to assign a score to correctly reflect analgesic needs, and its interpretation is subject to bias. OBJECTIVES: The study was done to validate a 4-point objective pain score (OPS) for the evaluation of acute postoperative pain and its comparison with the NRS. PATIENT AND METHODS: A total of 1021 paired readings of the OPS and NRS of 93 patients who underwent laparotomy and used patient-controlled analgesia were evaluated. Acute pain service (APS) personnel recorded the OPS and NRS. Rescue analgesia was divided into two incremental levels (level 1-paracetamol 1 g for NRS 2 - 5 and OPS 3, Level 2-Fentanyl 25 mcg for NRS ≥ 6 and OPS 1 and 2). In cases of disagreement between the two scores, an independent consultant decided the rescue analgesia. RESULTS: The NRS and OPS agreed across the range of pain. There were 25 disagreements in 8 patients. On 24 occasions, rescue analgesia was increased from level 1 to 2, and one occasion it was decreased from level 2 to 1. On all 25 occasions, the decision to supplement analgesia went in favor of the OPS over the NRS. Besides these 25 disagreements, there were 17 occasions in which observer bias was possible for level 2 rescue analgesia. CONCLUSIONS: The OPS is a good stand-alone pain score and is better than the NRS for defining mild and moderate pain. It may even be used to supplement NRS when it is indicative of mild or moderate pain.

Transesophageal echocardiography probe shutdown in a patient with hyperthermia.

The use of transesophageal echocardiography (TEE) has been increasing over the past few years. It is considered a semi-invasive monitor and a safe diagnostic device. Though complications are rare, they must be known to operators who frequently perform TEE. TEE probes are known to cause tissue heating and damage on prolonged use. In this case report, we describe shutdown of the transesophageal probe in our patient with high-grade fever.