Investigating the effectiveness of oral ketamine on pain, mood and quality of life in treatment resistant chronic pain.

Introduction: Chronic pain is defined as pain lasting longer than 3 months. This often causes persistent emotional distress and functional disability that is refractory to conventional treatments. Emerging evidence suggests that oral Ketamine therapy may have a specific role in managing treatment-resistant chronic pain. This study aimed to assess the effectiveness of oral ketamine within a tertiary chronic pain management clinic. Methods: This study was a clinic-based retrospective descriptive study of 79 patients with a broad range of chronic pain diagnoses and treated with oral ketamine over a period up to 12 years. Changes in pain, mood and quality of life (QoL) were assessed using a numerical pain severity score, the Brief Pain Inventory (BPI), the Public Health Questionnaire (PHQ-9) and American Chronic Pain Association Quality of Life (QoL) scale. Results: 73 patients were accessible for follow-up (mean daily dose and treatment duration were 193.84 mg and 22.6 months respectively). Pain scores decreased (p < 0.0001) on both numerical scores (41.6% decrease) and BPI scoring (mean decrease 2.61). Mood improved (p < 0.0001) across both PHQ-9 and BPI measurements. Patients also reported less difficulty with daily activities and improved QoL. The most common adverse reaction was drowsiness (21.9%), with 30.1% reporting no adverse reactions from Ketamine. Discussion: This work adds to the growing body of evidence that under the supervision of a pain specialist, oral ketamine therapy may be a safe, tolerable and effective treatment for chronic pain conditions which have not responded to other management options. Further research is required to produce a more accurate understanding of its chronic use. Key message: This real-world study shows that patients being treated with oral ketamine for chronic pain report decreased severity of pain, improved mood and increased quality of life across all conditions.

Prevalence of Bleeding and Thrombosis in Critically Ill Patients with Chronic Liver Disease.

INTRODUCTION: Hemorrhage and venous thromboembolism (VTE) are recognized complications of chronic liver disease (CLD), but their prevalence and risk factors in critically ill patients are uncertain. PATIENTS AND METHODS: We studied a retrospective cohort of patients with CLD nonelectively admitted to a specialist intensive care unit (ICU) determining the prevalence and timing of major bleeding and VTE (early, present on admission/diagnosed within 48 hours; later, diagnosed >48 hours post-ICU admission). Associations with baseline clinical and laboratory characteristics, multiorgan failure (MOF), blood product administration, and mortality were explored. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: Of 623 patients with median age 52, bleeding (>48 hours after admission) occurred in 87 (14%) patients. Bleeding was associated with greater illness severity and increased mortality. Gastrointestinal bleeding accounted for 72% of events, secondary to portal hypertension in >90%. Procedure-related bleeding was uncommon. VTE occurred in 125 (20%) patients: early VTE in 80 (13%) and involving the portal vein in 85%. Later VTE affected 45 (7.2%) patients. Hepatocellular carcinoma (HCC) and nonalcoholic liver disease were independently associated with early VTE (OR: 2.79, 95% CI: 1.5-5.2 and OR: 2.32, 95% CI: 1.4-3.9, respectively), and HCC, sepsis, and cryoprecipitate use with late VTE (OR: 2.45, 95% CI: 1.11-5.43; OR: 2.26, 95% CI: 1.2-4.3; and OR: 2.60, 95% CI: 1.3-5.1). CONCLUSION: VTE was prevalent on admission to critical care and less commonly developed later. Bleeding was associated with MOF and increased mortality. Severe MOF was not associated with an increased rate of VTE which was linked with HCC, and specific etiologies of CLD.

A Liver's Iliad: Liver Graft Retransplant to a Second Recipient After Brain Death in a First Recipient.

With the current increased incidence of cirrhosis, the demand for liver transplant continues to grow. Here, we performed a systematic review to assess the feasibility, safety, and long-term outcomes of reused liver grafts for expansion of the donor pool. Our search identified 19 studies, including 36 patients plus 1 patient from our own institution. Ten studies were single case reports, 4 were case series, 4 were letters to the editor, and 1 was a literature review and also included a case report. Our patient presented with intentional acetaminophen overdose, received a transplant from a brain dead donor, and was confirmed brain dead 12 days posttransplant. The second recipient, who had alcoholrelated liver disease cirrhosis, underwent orthotopic liver transplant with the reused liver and was discharged from the hospital after an uneventful postoperative course. Among the 19 studies, all donors had confirmed brain death and all transplants included the whole liver, except for 2 cases of auxiliary liver grafts (reduced liver transplant) and 1 case of extended right living-donor liver graft (donor and recipient being related sisters). Overall, among first recipients, the most frequent cause of liver disease was acetaminophen overdose followed by alcohol-related liver disease cirrhosis. There were 2 cases of retransplant. Among second recipients, hepatocellular carcinoma was the most frequent cause of liver disease followed by alcohol-related liver disease cirrhosis. We found that functional outcomes with these grafts were comparable to outcomes with grafts from conventional donors; in the absence of other contraindications, we suggest that, not only for liver transplant but for other organs, these reused grafts can be used for those awaiting transplantation. Because the ability to reuse grafts is an infrequent condition, it would be difficult to generally recommend this technique; however, on a case-by-case basis, this source could expand the donor pool.

Intraoperative Monitoring of the Obese Patient Undergoing Surgery: A Narrative Review.

With the increasing prevalence of obesity in the population, anaesthetists must confidently manage both the pathophysiological and technical challenges presented in bariatric and non-bariatric surgery. The intraoperative period represents an important opportunity to optimise and mitigate risk. However, there is little formal guidance on what intraoperative monitoring techniques should be used in this population. This narrative review collates the existing evidence for intraoperative monitoring devices in the obese patients. Although a number of non-invasive blood pressure monitors have been tested, an invasive arterial line remains the most reliable monitor if accurate, continuous monitoring is required. Goal-directed fluid therapy is recommended by clinical practice guidelines, but the methods tested to assess this had guarded applicability to the obese population. Transcutaneous carbon dioxide (CO2) monitoring may offer additional benefit to standard capnography in this population. Individually titrated positive end expiratory pressure (PEEP) and recruitment manoeuvres improved intraoperative mechanics but yielded no benefit in the immediate postoperative period. Depth of anaesthesia monitoring appears to be beneficial in the perioperative period regarding recovery times and complications. Objective confirmation of reversal of neuromuscular blockade continues to be a central tenet of anaesthesia practice, particularly relevant to this group who have been characterised as an "at risk" extubation group. Where deep neuromuscular blockade is used, continuous neuromuscular blockade is suggested. Both obesity and the intraoperative context represent somewhat unstable search terms, as the clinical implications of the obesity phenotype are not uniform, and the type and urgency of surgery have significant impact on the intraoperative setting. This renders the generation of summary conclusions around what intraoperative monitoring techniques are suitable in this population highly challenging.

Prevention of Cardiac Surgery-Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial.

BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

Biomarker-guided implementation of the KDIGO guidelines to reduce the occurrence of acute kidney injury in patients after cardiac surgery (PrevAKI-multicentre): protocol for a multicentre, observational study followed by randomised controlled feasibility trial.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial. METHODS AND ANALYSIS: We plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes. ETHICS AND DISSEMINATION: The PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial. TRIAL REGISTRATION NUMBER: NCT03244514.

A Multinational Observational Study Exploring Adherence With the Kidney Disease: Improving Global Outcomes Recommendations for Prevention of Acute Kidney Injury After Cardiac Surgery.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] ±1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD ±1.1] vs 3.5 [SD ±1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.

Irish Maternal Early Warning Score.

Early Warning Systems (EWS) track the physiological parameters of individual patients and trigger a response when the parameter threshold has been reached. The use of early warning scores in adult hospital medicine has been shown to be beneficial in facilitating the early recognition of the deteriorating patient, thereby enabling prompt treatment. In 2012, a standardised National Early Warning Score was introduced in Ireland for all non-pregnant patients. The 2007 Confidential Enquiry into Maternal and Child Health recommended that EWS be introduced into maternity practice. However, the unique physiological changes of pregnancy even in health means that any scoring system must be specially adapted. The Obstetric Early Warning Score (OEWS) aims to promote early recognition of the pregnant patient at risk of deterioration. In 2013, a standardised Irish Maternity Early Warning System (IMEWS) was introduced nationally. However, the scoring system is only part of the package, once triggered it needs to be effectively communicated and acted upon promptly by appropriately trained clinicians. Despite undoubted shortcomings, the international evidence to date is supportive of the beneficial role of the OEWS in preventing maternal morbidity. Further research is needed to improve the sensitivity and specificity of the OEWS and how to better integrate it into every-day clinical practice.

Erector Spinae Plane Blocks in Major Hepatopancreaticobiliary Surgery: A Case Series.

Hepatopancreaticobiliary (HPB) surgery is major upper abdominal surgery with considerable risk of pulmonary complications related to postoperative pain. While epidural analgesia remains an effective analgesic technique for upper abdominal surgery, HPB surgery poses challenges to its use due to coagulopathy. Erector spinae plane (ESP) blocks are a promising alternative to epidurals. Injection of local anesthetic deep to the erector spinae muscle plane and placement of a catheter for prolonged effect provide both somatic and visceral analgesia for both thoracic and abdominal surgery. We describe a series of 3 cases that illustrate the efficacy of ESP blocks after major HPB surgery.