Perioperative fluid management and outcomes in adult deceased donor liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: Fluid management practices during and after liver transplantation vary widely among centers despite better understanding of the pathophysiology of end-stage liver disease and of the effects of commonly used fluids. This reflects a lack of high quality trials in this setting, but also provides a rationale for both systematic review of all relevant studies in liver recipients and evaluation of new evidence from closely related domains, including hepatology, non-transplant abdominal surgery, and critical care. OBJECTIVES: To develop evidence-based recommendations for perioperative fluid management to optimize immediate and short-term outcomes following liver transplantation. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies included those evaluating the following postoperative outcomes: acute kidney injury, respiratory complications, operative blood loss/red cell units required, and intensive care length of stay. PROSPERO protocol ID: CRD42021241392 RESULTS: Following expert panel review, 18 of 1624 screened studies met eligibility criteria for inclusion in the final quantitative synthesis. These included six single center RCTs, 11 single center observational studies, and one observational study comparing centers with different fluid management techniques. Definitions of interventions and outcomes varied between studies. Recommendations are therefore based substantially on expert opinion and evidence from other clinical settings. CONCLUSIONS: A moderately restrictive or "replacement only" fluid regime is recommended, especially during the dissection phase of the transplant procedure. Sustained hypervolemia, based on absence of fluid responsiveness, elevated filling pressures and/or echocardiographic findings, should be avoided (Quality of Evidence: Moderate | Grade of Recommendation: Weak for restrictive fluid regime. Strong for avoidance of hypervolemia). Mean Arterial Pressure (MAP) should be maintained at >60-65 mmHg in all cases (Quality of Evidence: Low | Grade of Recommendation: Strong). There is insufficient evidence in this population to support preferential use of any specific colloid or crystalloid for routine volume replacement. However, we recommend against the use of 130/.4 HES given the high incidence of AKI in this population.

The ability of pulse oximetry-derived peripheral perfusion index to detect fluid responsiveness in patients with septic shock.

BACKGROUND: Fluid challenge test is a widely used method for the detection of fluid responsiveness in acute circulatory failure. However, detection of the patient's response to the fluid challenge requires monitoring of cardiac output which is not feasible in many settings. We investigated whether the changes in the pulse oximetry-derived peripheral perfusion index (PPI), as a non-invasive surrogate of cardiac output, can detect fluid responsiveness using the fluid challenge test or not. METHODS: We prospectively enrolled 58 patients with septic shock on norepinephrine infusion. Fluid challenge test, using 200 mL crystalloid solution, was performed in all study subjects. All patients received an additional 300 mL crystalloid infusion to confirm fluid responsiveness. Velocity time integral (VTI) (using transthoracic echocardiography), and PPI were measured at the baseline, after 200 mL fluid challenge, and after completion of 500 mL crystalloids. Fluid responsiveness was defined by 10% increase in the VTI after completion of the 500 mL. The predictive ability of ∆PPI [Calculated as (PPI after 200 mL - baseline PPI)/baseline PPI] to detect fluid responders was obtained using the receiver operating characteristic curve. RESULTS: Forty-two patients (74%) were fluid responders; in whom, the mean arterial pressure, the central venous pressure, the VTI, and the PPI increased after fluid administration compared to the baseline values. ∆PPI showed moderate ability to detect fluid responders [area under receiver operating characteristic curve (95% confidence interval) 0.82 (0.70-0.91), sensitivity 76%, specificity 80%, positive predictive value 92%, negative predictive value 54%, cutoff value ≥ 5%]. There was a significant correlation between ∆PPI and ∆VTI induced by the fluid challenge. CONCLUSION: ∆PPI showed moderate ability to detect fluid responsiveness in patients with septic shock on norepinephrine infusion. Increased PPI after 200 mL crystalloid challenge can detect fluid responsiveness with a positive predictive value of 92%; however, failure of the PPI to increase does not exclude fluid responsiveness. CLINICAL TRIAL IDENTIFIER: NCT03805321. Date of registration: 15 January 2019. Clinical trial registration URL: https://clinicaltrials.gov/ct2/show/NCT03805321?term=ahmed+hasanin&rank=9 .

Validation of electrical velocimetry in resuscitation of patients undergoing liver transplantation. Observational study.

Major hemodynamic changes are frequently noted during liver transplantation (LT). We evaluated the performance of electrical velocimetry (EV) as compared to that of TEE in SV optimization during liver transplantation. This was an observational study in 32 patients undergoing LT. We compared SV values measured simultaneously by EV (SVEV) and TEE (SVTEE) at baseline 30 min after induction, at the end of dissection phase, 30 min after anhepatic phase, 30 min after reperfusion. We also evaluated the reliability of EV to track changes In SV before and after 49 fluid challenges. Finally, the SV variation (SVV) and pulse pressure variation (PPV) were tested as predictors for volume responsiveness, defined as an increase in SV ≥ 10% after 250 ml of colloid. For 112 paired SV data, the overall correlation was 0.76 and bias (limits of agreement) 0.3 (- 29 to 29) ml percentage error 62%. The EV was able to track changes in SV with a concordance rate of 97%, and a sensitivity and specificity of 93% to detect a positive fluid challenge. The AUC values (with 95% confidence intervals) for SVV and PPV were 0.68 (0.52-0.83) and 0.72 (0.57-0.86), respectively, indicating low predictive capacity in these setting. The absolute values of SV derived from EV did not agree with SV derived from TEE. However, EV was able to track the direction of changes in SV during hemodynamic management of patients undergoing liver transplantation.Clinical trial registration: Clinicaltrials.gov Identifier: NCT03228329 prospectively Registered on 13-July-2017.

Diagnostic values of CD64, C-reactive protein and procalcitonin in ventilator-associated pneumonia in adult trauma patients: a pilot study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infections; however, its diagnosis remains difficult to establish in the critical care setting. We investigated the potential role of neutrophil CD64 (nCD64) expression as an early marker for the diagnosis of VAP. METHODS: Forty-nine consecutive patients with clinically suspected VAP were prospectively included in a single-center study. The levels of nCD64, C-reactive protein (CRP), and serum procalcitonin (PCT) were analyzed for diagnostic evaluation at the time of intubation (baseline), at day 0 (time of diagnosis), and at day 3. The receiver operating characteristic curves were analyzed to identify the ideal cutoff values. RESULTS: VAP was confirmed in 36 of 49 cases. In patients with and without VAP, the median levels (interquartile range, IQR) of nCD64 did not differ either at baseline [2.4 (IQR, 1.8-3.1) and 2.6 (IQR, 2.3-3.2), respectively; p=0.3] or at day 0 [2 (IQR, 2.5-3.0) and 2.6 (IQR, 2.4-2.9), respectively; p=0.8]. CRP showed the largest area under the curve (AUC) at day 3. The optimum cutoff value for CRP according to the maximum Youden index was 133 mg/dL. This cutoff value had 69% sensitivity and 76% specificity for predicting VAP; the AUC was 0.73 (95% CI, 0.59-0.85). The nCD64 and PCT values could not discriminate between the VAP and non-VAP groups either at day 0 or day 3. CONCLUSIONS: The results of this pilot study suggest that neutrophil CD64 measurement has a poor role in facilitating the diagnosis of VAP and thus may not be practically recommended to guide the administration of antibiotics when VAP is suspected.

Best Practices in Nuclear Imaging for the Diagnosis of Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in KSA: The Eagle Eyes of Local Experts.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart muscle. Variable symptoms of ATTR-CM can lead to a delayed diagnosis. Recognizing the diagnostic indicators is crucial to promptly detect this condition. A targeted literature review was conducted to examine the latest international consensus recommendations on a comprehensive diagnosis of ATTR-CM. Additionally, a panel consisting of nuclear medicine expert consultants (n = 10) and nuclear imaging technicians (n = 2) convened virtually from the Kingdom of Saudi Arabia (KSA) to formulate best practices for ATTR-CM diagnosis. The panel reached a consensus on a standard diagnostic pathway for ATTR-CM, which commences by evaluating the presence of clinical red flags and initiating a cardiac workup to assess the patient's echocardiogram. Cardiac magnetic resonance imaging may be needed, in uncertain cases. When there is a high suspicion of ATTR-CM, patients undergo nuclear scintigraphy and hematologic tests to rule out primary or light-chain amyloidosis. The expert panel emphasized that implementing best practices will support healthcare professionals in KSA to improve their ability to detect and diagnose ATTR-CM more accurately and promptly. Diagnosing ATTR-CM accurately and early can reduce morbidity and mortality rates through appropriate treatment.

Role of dexmedetomidine in modifying immune paralysis in patients with septic shock: randomized controlled trial.

BACKGROUND: Immune paralysis can be defined as a hypoinflammatory state associated with the incapacity of the immune system to release proinflammatory mediators despite the clearance of pathogens by antimicrobials. Persistent immune paralysis leads to failure to eradicate primary infections with a substantial increase in the risk of multiorgan dysfunction and mortality. The state of immune paralysis is caused mainly by the diminished ability of monocytes to release proinflammatory cytokines in response to endotoxin. This phenomenon is known as endotoxin tolerance. This study aimed to assess the role of dexmedetomidine in modifying immune paralysis in septic shock patients. METHODS: Twenty-four patients with septic shock were randomized into two groups of 12 patients. A continuous intravenous infusion of dexmedetomidine started at 0.15 µg kg-1 hr-1 and adjusted by 0.15 µg kg-1 h-1 to a maximum of 0.75 µg kg-1 h-1 (10 ml h-1), while midazolam was started at 1 mg h-1 (2 mL hr-1) and adjusted by 1 mg h-1 to a maximum of 5 mg h-1 (10 mL h-1). All infusions were adjusted by increments of 2 mL/hr-1 to maintain blinding. Serum levels of CD42a+/CD14+, HLADR+/CD14+, CRP, IL-6, IL-10 and TNF-α were measured at baseline (T1), 12 h (T2), and 24 h (T3). RESULTS: Treatment with dexmedetomidine yielded no significant difference in CD42a+/CD14+, HLADR+/CD14, CD24b-MFI, HLADR-MFI, IL6 and TREM1 at all time points when compared with midazolam treatment. There was no significant difference in TLR levels between the two groups. Cardiac output in the dexmedetomidine group showed a significant decrease at 6, 12 and 24 h (P = 0.033, 0.021, and 0.005, respectively) compared with that in the midazolam group. CONCLUSION: Our results indicated that dexmedetomidine did not affect CD42a+/CD14+ and HLA-DR+/CD14+ expression in septic patients. Furthermore, cytokine production and inflammatory biomarkers did not change with dexmedetomidine infusion. Trial registration Clinical trial.gov registry (NCT03989609) on June 14, 2019, https://register. CLINICALTRIALS: gov .

Effect of norepinephrine on blood volume, cardiac output, and systemic filling pressure in patients undergoing liver transplantation.

BACKGROUND: Patients with liver cirrhosis develop symptoms comparable to those of patients with sepsis, who have increased total vascular compliance, which may cause blood pooling in the venous pool. No previous studies have evaluated the effect of using norepinephrine on the intravascular blood volume. We investigated the norepinephrine infusion's effect on the mean systemic filling pressure, venous return, and cardiac preload in patients undergoing liver transplantation. METHODS: Overall, 33 patients who underwent living donor liver transplantation were included in this study. Cardiac output (CO) was measured using a PiCCO device (Pulsion Medical Systems, Munich, Germany). The mean systemic filling pressure was calculated using the inspiratory hold maneuver at four time intervals - at baseline, 10 min after the norepinephrine infusion, 5 min after norepinephrine discontinuation, and after infusion of 500 cc of 5% albumin. Other hemodynamic parameters, including the mean arterial pressure (MAP), pulse pressure variation, stroke volume variation, global end-diastolic volume, and mitral inflow velocity (E wave), were also evaluated. RESULTS: The norepinephrine infusion increased MAP and systemic vascular resistance in all patients. Moreover, it increased CO, mean systemic filling pressure, and global end-diastolic volume in 20 patients (60%), whereas there were no changes in these variables in 13 patients (40%). In all patients, norepinephrine infusion discontinuation caused a significant decrease in MAP, CO, resistance to venous return, and mean systemic filling pressure. Infusion of 500 cc colloid increased CO; however, interestingly, it was associated with a significant decrease in systemic vascular resistance; hence, MAP and mean systemic filling pressure showed no changes. CONCLUSIONS: The norepinephrine infusion at 0.1 µg-1 kg-1 min-1 was associated with an increase in CO in patients with liver cirrhosis undergoing liver transplantation. Norepinephrine's effect on CO was primarily attributable to an increase in venous return due to an increase in mean systemic filling pressure.

Evaluation of Diaphragmatic Ultrasound Indices as Predictors of Successful Liberation From Mechanical Ventilation in Subjects With Abdominal Sepsis.

BACKGROUND: Sepsis-induced diaphragmatic dysfunction is one of the main risk factors of failure to liberate patients from mechanical ventilation. Several studies addressed diaphragmatic ultrasound as a valuable tool in the assessment of diaphragmatic function during liberation from mechanical ventilation in different populations. However, none of these studies examined the use of diaphragmatic ultrasound to predict failure of liberation from mechanical ventilation in subjects with sepsis METHODS: A prospective observational study was done with subjects on mechanical ventilation and with abdominal sepsis. The diaphragmatic thickening fraction, diaphragmatic excursion, and rapid shallow breathing index were assessed 30 min after a spontaneous breathing trial RESULTS: Thirty subjects were enrolled in the study. Seventeen subjects were successfully extubated (56.6%), whereas extubation failed in 13 subjects (43.4%). The time to the first liberation attempt was significantly shorter in the liberation-success group 2.3 (0.7) d compared with the liberation-failure group 5.8 (4.7) d; P = .02. The optimum cutoff value of diaphragmatic thickening fraction for predicting liberation success was ≥30.7%, with a sensitivity of 94.1% and a specificity of 100%. The area under the curve was 0.977. Although diaphragmatic excursion of ≥10.4 mm had a sensitivity of 94% and a specificity of 85% for predicting liberation success, with an area under the curve of 0.85. A rapid shallow breathing index of ≤44 had a specificity of 100% and a sensitivity of 76%; the area under the curve was 0.9. CONCLUSIONS: Diaphragmatic ultrasound indices, namely diaphragmatic thickening fraction and diaphragmatic excursion, could be useful parameters for assessment of success of liberation in patients on mechanical ventilation with abdominal sepsis. (ClinicalTrials.gov registration NCT03094299.).

The therapeutic potential of intraoperative hypercapnia during video-assisted thoracoscopy in pediatric patients.

BACKGROUND: Although the cardiovascular effect of CO2 insufflation has not been reported in pediatric thoracoscopy, several clinical trials have demonstrated significant hemodynamic deterioration in adults. We investigated the concept of therapeutic hypercapnia for counteracting the hemodynamic effect of induced capnothorax. METHODS: Twelve pediatric patients who underwent video-assisted thoracoscopic patent ductus arteriosus closure were enrolled in the study. Cardiorespiratory variables were determined during baseline T1 and after CO2 insufflation at pressures of 2 mm Hg T2, 4 mm Hg T3, 6 mm Hg T4, 8 mm Hg T5, and 10 mm Hg T6. RESULTS: CO2 insufflation was not associated with any adverse hemodynamic effects. Cardiac output and central venous oxygen saturation increased progressively throughout the study protocol. Relative to baseline peak velocity, systolic flow time corrected for heart rate, heart rate, and central venous pressure increased significantly during insufflation, but systolic and diastolic blood pressure remained unchanged. Arterial CO2 increased from 40.7 +/- 3 at T1 to 61 +/- 1.6 at T6 mm Hg. Arterial oxygen tension increased from 170.9 +/- 3.3 at T1 to 182 +/- 2 at T6; arterial PH decreased from 7.31 +/- 1.2 at T1 to 7.14 +/- 4.6 at T6. CONCLUSION: Hypercapnia targeting CO2 50-70 mm Hg was associated with increased cardiac output, central venous O2, and arterial O2 tension in patients undergoing video-assisted thoracoscopic patent ductus arteriosus closure using one-lung ventilation without any deleterious cardiopulmonary effects.

Perioperative Coagulation Management in Liver Transplant Recipients.

We review contemporary coagulation management for patients undergoing liver transplantation. A better understanding of the complex physiologic changes that occur in patients with end-stage liver disease has resulted in significant advances in anesthetic and coagulation management. A group of internationally recognized experts have critically evaluated current approaches for coagulopathy detection and management. Strategies for blood component and factor replacement have been evaluated and recommended therapies proposed. Pharmacologic treatment and prevention of coagulopathy, management of patients receiving antiplatelet medications, and the role of transesophageal echocardiography for early detection and management of thromboses are presented.

The critically ill patient with tuberculosis in intensive care: Clinical presentations, management and infection control.

Tuberculosis (TB) is one of the top ten causes of death worldwide. In 2016, there were 490,000 cases of multi-drug resistant TB globally. Over 2 billion people have asymptomatic latent Mycobacterium tuberculosis infection. TB represents an important, but neglected management issue in patients presenting to intensive care units. Tuberculosis in intensive care settings may present as the primary diagnosis (active drug sensitive or resistant TB disease). In other patients TB may be an incidental co-morbid finding as previously undiagnosed sub-clinical or latent TB which may re-activate under conditions of stress and immunosuppression. In Sub-Saharan Africa, where co-infection with the human immunodeficiency virus and other communicable diseases is highly prevalent, TB is one of the most frequent clinical management issues in all healthcare settings. Acute respiratory failure, septic shock and multi-organ dysfunction are the most common reasons for intensive care unit admission of patients with pulmonary or extrapulmonary TB. Poor absorption of anti-TB drugs occurs in critically ill patients and worsens survival. The mortality of patients requiring intensive care is high. The majority of early TB deaths result from acute cardiorespiratory failure or septic shock. Important clinical presentations, management and infection control issues regarding TB in intensive care settings are reviewed.

The use of dexmedetomidine in pediatric cardiac surgery.

We tested dexmedetomidine, an alpha2 agonist, for its ability to decrease heart rate, arterial blood pressure, and neuroendocrinal responses during pediatric cardiac surgery. In a randomized, placebo-controlled study, 30 pediatric patients undergoing open heart surgery were randomly assigned to one of two equal groups. The control group received saline, whereas the treatment group (DEX group) received an initial bolus dose of dexmedetomidine (0.5 microg/kg) over 10 min, followed immediately by a continuous infusion of 0.5 microg.kg(-1).h(-1). Arterial blood pressure, heart rate, and sequential concentrations of circulating cortisol, epinephrine, norepinephrine, and blood glucose were measured. Relative to baseline, arterial blood pressure and heart rate decreased significantly after the administration of dexmedetomidine through skin incision. In the control group, patients' heart rate and arterial blood pressure measures increased after skin incision until the end of bypass (P < 0.05). In both groups, plasma cortisol, epinephrine, norepinephrine, and blood glucose increased significantly relative to baseline, after sternotomy, and after bypass. However, the values were significantly higher in the control group compared with the DEX group (P < 0.05). In conclusion, intraoperative dexmedetomidine infusion attenuated the hemodynamic and neuroendocrinal response to surgical trauma and cardiopulmonary bypass in pediatric patients undergoing corrective surgery for congenital heart disease.

Fungal infections in liver transplant patients admitted to the intensive care unit.

BACKGROUND: Fungal infections have a significant impact on patient survival after liver transplantation, mostly caused by Candida and Aspergillus. The clinical manifestations vary, and range from colonization, active local infection, to severe invasive form. A high degree of suspicion is required for the early diagnosis and, accordingly, the optimal management of these infections. This study aimed to evaluate fungal infection in the Intensive care Unit (ICU) in admitted liver transplant patients, focussing of etiologic agent, clinical/laboratory presentation (including mortality), and risk factors. MATERIAL AND METHODS: This retrospective study included living related liver transplanted patients admitted to the ICU. Clinical data was collected, thorough clinical evaluation was done, and laboratory tests were performed. Microbiological examination detecting the presence of fungus in various samples, using cultures and serology, and imaging investigations were carried out in all patients. RESULTS: This study included 23 cases of ICU-admitted liver transplant patients who were diagnosed with fungal infection. Candida was the most common fungal infection and occurred at a mean of 2 months after transplantation; while Aspergillus was less common and occurred later with worse laboratory findings. Invasive fungal infection constituted 43% of the diagnosed cases. Difference in mortality between Aspergillus and Candida was insignificant, as was difference between patients with and without fungal infection. CONCLUSIONS: Fungal infection among LT patients was common, including the invasive forms.

Unusual complication during pediatric thoracoscopy.

A small infant with congenital cystic adenomatoid was scheduled for thoracoscopic resection of the lung cyst. During carbon dioxide insufflation, there was a sharp rise of endtidal carbon dioxide which was followed by marked hypoxemia and bradycardia due to occlusion of the tracheal tube with blood. The plan changed to open thoracotomy and total pneumonectomy. Despite several reports, which addressed successful thoracoscopic cystic lung resection, its safety remain to be determined.

Surgical treatment of thoracic and lumbar tuberculosis by anterior interbody fusion and posterior instrumentation.

OBJECTIVE: To evaluate the efficacy and clinical outcome of simultaneous or sequential anterior and posterior surgical approaches in the management of spinal tuberculosis in the form of anterior extirpation of the tuberculous lesion, strut bone grafting of the defect produced and posterior instrumentation for spinal fixation. SUBJECTS AND METHODS: Twenty-two patients who had tuberculosis of the thoracic and lumbar spine with moderate to severe localized kyphosis and variable degrees of neurological deficits were treated at Al Razi Hospital (Kuwait) in the period from 1998 to 2000 by anterior debridement and autogenous strut bone grafting with simultaneous or staged posterior spinal fixation using either USS or SOCON spinal instrumentation. Appropriate antituberculosis treatment was given to all patients for 9-12 months. The postoperative follow-up period was 18 months. RESULTS: Of the 22 cases the average of preoperative kyphosis was 42 degrees. The average of immediate postoperative correction was 27 degrees. At the last follow-up the average correction was 24 degrees and the loss of correction did not exceed 3 degrees. Average fusion times were 5 months for one-segment fusions and 8 months for two-segment fusions. There was no recurrence of the disease in any of the cases. CONCLUSION: Posterior instrumental stabilization and anterior interbody fusion were found to be effective in arresting the disease, correcting kyphotic deformity and maintaining correction until solid spinal fusion.