Neuromuscular blockade in patients with ARDS: a rapid practice guideline.

The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) is to formulate an evidence-based guidance for the use of neuromuscular blocking agents (NMBA) in adults with acute respiratory distress syndrome (ARDS). The panel comprised 20 international clinical experts from 12 countries, and 2 patient representatives. We adhered to the methodology for trustworthy clinical practice guidelines and followed a strict conflict of interest policy. We convened panelists through teleconferences and web-based discussions. Guideline experts from the guidelines in intensive care, development, and evaluation Group provided methodological support. Two content experts provided input and shared their expertise with the panel but did not participate in drafting the final recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence and grade recommendations and suggestions. We used the evidence to decision framework to generate recommendations. The panel provided input on guideline implementation and monitoring, and suggested future research priorities. The overall certainty in the evidence was low. The ICM-RPG panel issued one recommendation and two suggestions regarding the use of NMBAs in adults with ARDS. Current evidence does not support the early routine use of an NMBA infusion in adults with ARDS of any severity. It favours avoiding a continuous infusion of NMBA for patients who are ventilated using a lighter sedation strategy. However, for patients who require deep sedation to facilitate lung protective ventilation or prone positioning, and require neuromuscular blockade, an infusion of an NMBA for 48 h is a reasonable option.

Diagnosis of death using neurological criteria in adult patients on extracorporeal membrane oxygenation: Development of UK guidance.

The diagnosis of death using neurological criteria is an important legal method of establishing death in the UK. The safety of the diagnosis lies in the exclusion of conditions which may mask the diagnosis and the testing of the fundamental reflexes of the brainstem including the apnoea reflex. Extracorporeal membrane oxygenation for cardiac or respiratory support can impact upon these tests, both through drug sequestration in the circuit and also through the ability to undertake the apnoea test. Until recently, there has been no nationally accepted guidance regarding the conduct of the tests to undertake the diagnosis of death using neurological criteria for a patient on extracorporeal membrane oxygenation. This article considers both the background to and the process of guideline development.

A narrative review of the impact of surgery and anaesthesia on acute kidney injury.

The epidemiology of peri-operative acute kidney injury varies depending on the definition, type of surgery and acute and chronic comorbidities. Haemodynamic instability, disturbance of the microcirculation, endothelial dysfunction, inflammation and tubular cell injury are the main factors contributing to the pathogenesis. There are no specific therapies. The most effective strategies to protect renal function during the peri-operative period are: the avoidance of nephrotoxic insults; optimisation of haemodynamics; prevention of hypotension; and meticulous fluid management, including avoidance of both hypovolaemia and hypervolaemia. Peri-operative acute kidney injury is associated with an increased risk of short- and long-term postoperative complications, including a longer stay in hospital, development of premature chronic kidney disease and increased mortality. Resource utilisation and healthcare costs are also higher. In future, the development of advanced clinical prediction scores, new imaging and monitoring techniques and the application of new biomarkers for acute kidney injury have the prospect of identifying acute kidney injury earlier and allowing a more personalised management approach with the aim of reducing the global burden of acute kidney injury.

Acute kidney injury as a risk factor of hyperactive delirium: A case control study.

PURPOSE: Delirium and acute kidney injury (AKI) are common organ dysfunctions during critical illness. Both conditions are associated with serious short- and long-term complications. We investigated whether AKI is a risk factor for hyperactive delirium. METHODS: This was a single-centre case control study conducted in a 30 bedded mixed Intensive Care Unit in the UK. Hyperactive delirium cases were identified by antipsychotic initiation and confirmation of delirium diagnosis through validated chart review. Cases were compared with non-delirium controls matched by Acute Physiology and Chronic Health Evaluation II score and gender. AKI was defined by the KDIGO criteria. RESULTS: 142 cases and 142 matched controls were identified. AKI stage 3 was independently associated with hyperactive delirium [Odds ratio (OR) 5.40 (95% confidence interval (CI) 2.33-12.51]. Other independent risk factors were mechanical ventilation [OR 2.70 (95% CI 1.40-5.21)], alcohol use disorder [OR 5.80 (95% CI 1.90-17.72)], and dementia [OR 9.76 (95% CI 1.09-87.56)]. Hospital length of stay was significantly longer in delirium cases (29 versus 20 days; p = .004) but hospital mortality was not different. CONCLUSIONS: AKI stage 3 is independently associated with hyperactive delirium. Further research is required to explore the factors that contribute to this association.

Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section.

PURPOSE: Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. METHODS: International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: "AKI diagnosis and evaluation", "Medical management of AKI" and "Renal Replacement Therapy for AKI." Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. RESULTS: The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. CONCLUSION: Consensus was reached on a future research agenda for the AKI section of the ESICM.

Acute kidney injury in kidney transplant patients.

Managing kidney transplant patients in an acute medical unit can be challenging, as patients have a single functioning kidney, underlying chronic kidney disease, and are immunosuppressed. Transplant patients develop AKI for all usual reasons but the differential diagnosis is wider and includes specific problems, such as obstruction of a single functioning kidney, vascular thrombosis, rejection, drug toxicity and drug-induced thrombotic microangiopathy. Septic AKI is common but again, the differential diagnosis of sepsis is wider. Transplant patients are at higher risk of developing both community and opportunistic infections, especially in the first year after the transplant or after any increase in immunosuppressive medication. In addition, there is always a risk of rejection, especially in case of reduction of immunosuppressive medications. Therefore, any change in the immunosuppressive therapy should to be discussed with the transplant team to achieve an appropriate balance between avoiding rejection and preventing opportunistic infections.

Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017 : Expert opinion of the Working Group on Prevention, AKI section, European Society of Intensive Care Medicine.

BACKGROUND: Acute kidney injury (AKI) in the intensive care unit is associated with significant mortality and morbidity. OBJECTIVES: To determine and update previous recommendations for the prevention of AKI, specifically the role of fluids, diuretics, inotropes, vasopressors/vasodilators, hormonal and nutritional interventions, sedatives, statins, remote ischaemic preconditioning and care bundles. METHOD: A systematic search of the literature was performed for studies published between 1966 and March 2017 using these potential protective strategies in adult patients at risk of AKI. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, exposure to potentially nephrotoxic drugs and radiocontrast. Clinical endpoints included incidence or grade of AKI, the need for renal replacement therapy and mortality. Studies were graded according to the international GRADE system. RESULTS: We formulated 12 recommendations, 13 suggestions and seven best practice statements. The few strong recommendations with high-level evidence are mostly against the intervention in question (starches, low-dose dopamine, statins in cardiac surgery). Strong recommendations with lower-level evidence include controlled fluid resuscitation with crystalloids, avoiding fluid overload, titration of norepinephrine to a target MAP of 65-70 mmHg (unless chronic hypertension) and not using diuretics or levosimendan for kidney protection solely. CONCLUSION: The results of recent randomised controlled trials have allowed the formulation of new recommendations and/or increase the strength of previous recommendations. On the other hand, in many domains the available evidence remains insufficient, resulting from the limited quality of the clinical trials and the poor reporting of kidney outcomes.

Renal recovery after acute kidney injury.

Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality, chronic kidney disease (CKD) and cardiovascular events. The degree of renal recovery from AKI may substantially affect these long-term endpoints. Therefore maximising recovery of renal function should be the goal of any AKI prevention and treatment strategy. Defining renal recovery is far from straightforward due in part to the limitations of the tests available to assess renal function. Here, we discuss common pitfalls in the evaluation of renal recovery and provide suggestions for improved assessment in the future. We review the epidemiology of renal recovery and of the association between AKI and the development of CKD. Finally, we stress the importance of post-discharge follow-up of AKI patients and make suggestions for its incorporation into clinical practice. Summary key points are that risk factors for non-recovery of AKI are age, CKD, comorbidity, higher severity of AKI and acute disease scores. Second, AKI and CKD are mutually related and seem to have a common denominator. Third, despite its limitations full recovery of AKI may best be defined as the absence of AKI criteria, and partial recovery as a fall in AKI stage. Fourth, after an episode of AKI, serial follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression. Measures to promote recovery are similar to those preventing renal harm. Specific interventions promoting repair are still experimental.

The Dose Response Multicentre Investigation on Fluid Assessment (DoReMIFA) in critically ill patients.

BACKGROUND: The previously published "Dose Response Multicentre International Collaborative Initiative (DoReMi)" study concluded that the high mortality of critically ill patients with acute kidney injury (AKI) was unlikely to be related to an inadequate dose of renal replacement therapy (RRT) and other factors were contributing. This follow-up study aimed to investigate the impact of daily fluid balance and fluid accumulation on mortality of critically ill patients without AKI (N-AKI), with AKI (AKI) and with AKI on RRT (AKI-RRT) receiving an adequate dose of RRT. METHODS: We prospectively enrolled all consecutive patients admitted to 21 intensive care units (ICUs) from nine countries and collected baseline characteristics, comorbidities, severity of illness, presence of sepsis, daily physiologic parameters and fluid intake-output, AKI stage, need for RRT and survival status. Daily fluid balance was computed and fluid overload (FO) was defined as percentage of admission body weight (BW). Maximum fluid overload (MFO) was the peak value of FO. RESULTS: We analysed 1734 patients. A total of 991 (57 %) had N-AKI, 560 (32 %) had AKI but did not have RRT and 183 (11 %) had AKI-RRT. ICU mortality was 22.3 % in AKI patients and 5.6 % in those without AKI (p < 0.0001). Progressive fluid accumulation was seen in all three groups. Maximum fluid accumulation occurred on day 2 in N-AKI patients (2.8 % of BW), on day 3 in AKI patients not receiving RRT (4.3 % of BW) and on day 5 in AKI-RRT patients (7.9 % of BW). The main findings were: (1) the odds ratio (OR) for hospital mortality increased by 1.075 (95 % confidence interval 1.055-1.095) with every 1 % increase of MFO. When adjusting for severity of illness and AKI status, the OR changed to 1.044. This phenomenon was a continuum and independent of thresholds as previously reported. (2) Multivariate analysis confirmed that the speed of fluid accumulation was independently associated with ICU mortality. (3) Fluid accumulation increased significantly in the 3-day period prior to the diagnosis of AKI and peaked 3 days later. CONCLUSIONS: In critically ill patients, the severity and speed of fluid accumulation are independent risk factors for ICU mortality. Fluid balance abnormality precedes and follows the diagnosis of AKI.

Indications and management of mechanical fluid removal in critical illness.

BACKGROUND: The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to all aspects of fluid therapy, including the management of fluid overload (FO). The aim of the working subgroup 'Mechanical fluid removal' was to review the indications, prescription, and management of mechanical fluid removal within the broad context of fluid management of critically ill patients. METHODS: The working group developed a list of preliminary questions and objectives and performed a modified Delphi analysis of the existing literature. Relevant studies were identified through a literature search using the MEDLINE database and bibliographies of relevant research and review articles. RESULTS: After review of the existing literature, the group agreed the following consensus statements: (i) in critically ill patients with FO and with failure of or inadequate response to pharmacological therapy, mechanical fluid removal should be considered as a therapy to optimize fluid balance. (ii) When using mechanical fluid removal or management, targets for rate of fluid removal and net fluid removal should be based upon the overall fluid balance of the patient and also physiological variables, individualized, and reassessed frequently. (iii) More research on the role and practice of mechanical fluid removal in critically ill patients not meeting fluid balance goals (including in children) is necessary. CONCLUSION: Mechanical fluid removal should be considered as a therapy for FO, but more research is necessary to determine its exact role and clinical application.

Beyond the randomized clinical trial: citrate for continuous renal replacement therapy in clinical practice.

BACKGROUND: Premature circuit clotting is a major problem during continuous renal replacement therapy (CRRT). Six randomized controlled trials confirmed that regional anticoagulation with citrate is superior to heparin. Our objective was to compare circuit patency with citrate, heparin and epoprostenol in routine clinical practice. METHODS: We retrospectively analysed data on circuit patency of all circuits used in a single centre between September 2008 and August 2009. We differentiated between premature filter clotting, elective discontinuation and waste. RESULTS: 309 patients were treated with CRRT (n = 2,059 circuits). The mean age was 65.7; 63.8% were male. The methods to maintain circuit patency were unfractionated heparin (42.3%), epoprostenol (23.0%), citrate (14.7%), combinations of different anticoagulants (14.6%) and no anticoagulation (4.7%). Premature clotting was the most common reason for circuit discontinuation among circuits anticoagulated with heparin, epoprostenol or combinations of different anticoagulants (59-62%). Among circuits anticoagulated with citrate the main reason for discontinuation was elective (61%). Hazard regression analysis confirmed significantly better circuit survival with citrate. Changing from heparin to citrate decreased the risk of premature circuit clotting by 75.8%. CONCLUSION: In routine clinical practice, regional anticoagulation with citrate is associated with significantly better circuit patency than heparin or epoprostenol.

Predicting the development of acute kidney injury in liver cirrhosis--an analysis of glomerular filtration rate, proteinuria and kidney injury biomarkers.

BACKGROUND: The timely diagnosis of acute kidney injury (AKI) in liver cirrhosis is challenging. AIM: To evaluate whether quantification of glomerular filtration rate (GFR), proteinuria and kidney injury biomarkers can accurately predict the development of AKI. METHODS: A prospective cohort analysis of patients with cirrhosis was performed. Measures of baseline kidney function included serum creatinine, iohexol clearance and urine protein:creatinine ratio. Blood and urine samples were collected daily. A retrospective analysis of cystatin C GFR and neutrophil gelatinase-associated lipocalin (NGAL) measured 48 h prior to the diagnosis of AKI was undertaken to evaluate their ability to predict the development of AKI. RESULTS: Eighteen of the 34 cirrhosis patients studied developed AKI. A GFR <60 mL/min/1.73 m(2) was identified in 56% with Iohexol clearance compared to 8% using the four-variable modified diet in renal disease formula (P < 0.0001). Prediction of AKI, 48 h prior to the development of AKI with cystatin C GFR and serum NGAL concentration were similar; area under the receiver operating curve (AUROC) values 0.74 (0.51-0.97), P = 0.04 and 0.72 (0.52-0.92), P = 0.02 respectively. The development of AKI was strongly predicted by urine protein:creatinine ratio above the cut-off of >30 (equivalent to 300 mg/day of proteinuria) sensitivity 82% (57-96) and specificity 80% (52-96), AUROC 0.86 (0.73-0.98), P ≤ 0.0001. [OR 21 (3-133), P ≤ 0.002]. CONCLUSIONS: In patients with liver cirrhosis a urine protein:creatinine ratio >30 predicts AKI. Iohexol clearance and cystatin C formulae identify a greater proportion of patients with a GFR <60 mL/min/1.73 m(2), which also predicts the development of AKI.

Intravenous fluid use in the acutely unwell adult medical inpatient: improving practice through a clinical audit process.

BACKGROUND: Our Trust developed a clinical guideline to improve the prescribing and use of intravenous (IV) fluids based on the British consensus guidelines on IV fluid therapy for adult surgical patients. We audited the effect of targeted interventions to improve performance against this guideline. METHOD: There were 53 IV fluid prescription charts in the pre-intervention audit and 48 in the post-intervention audit. Data was collected on the seven local practice standards ('local gold standards') in the clinical guideline; compliance with all of them was necessary to meet the IV fluid prescribing bundle of care. RESULTS: The proportion of prescriptions which met the IV fluid prescribing bundle of care increased (3.8% to 22.9% [p=0.004]) and the legibility of the IV fluid prescription increased (28.3% to 56.3% [p=0.004]). CONCLUSION: We have shown that the process of prescribing, administering and monitoring IV fluid use can be significantly improved through a range of targeted multi-disciplinary interventions.

Challenges of defining acute kidney injury.

BACKGROUND: Until recently, there was a lack of a uniform definition for acute kidney injury (AKI). The 'acute renal injury/acute renal failure syndrome/severe acute renal failure syndrome' criteria, the Risk - Injury - Failure - Loss of kidney function - End stage renal disease (RIFLE) criteria and the Acute Kidney Injury Network (AKIN) classification were the most recent proposals. AIM: To compare the performance of the different AKI definitions. DESIGN AND METHODS: Application of the three most recent AKI definitions to 41 972 critically ill ICU patients and comparison of their performance. RESULTS: Incidence and outcome of AKI varied depending on the criteria. The RIFLE and AKIN classification led to similar total incidences of AKI (35.9 vs. 35.4%) but different incidences and outcomes of the individual AKI stages. Multivariate analysis showed that the different stages of AKI were independently associated with mortality. The worst stage of AKI was associated with an increased odds ratio for mortality of 1.59-2.27. Non-surgical admission, maximum number of associated failed organ systems, emergency surgery and mechanical ventilation were consistently associated with the highest risk of hospital mortality. The proposed AKI definitions differ in the cut-off values of serum creatinine, the suggested time frame, the approach towards patients with missing baseline values and the method of classifying patients on renal replacement therapy. All classifications can miss patients with definite AKI. CONCLUSION: The three most recent definitions of AKI confirmed a correlation between severity of AKI and outcome but have limitations and the potential to miss patients with definite AKI. These limitations need to be considered when using the criteria in clinical practice.

ICU and 6-month outcome of oncology patients in the intensive care unit.

BACKGROUND: Advances in oncological care have led to improved short- and long-term prognosis of cancer patients but admission to the intensive care unit (ICU) remains controversial. AIM: The objective was to assess the outcome of patients with haematological malignancies and solid tumours admitted to the ICU as emergencies, and to identify risk factors for mortality. DESIGN AND METHODS: Retrospective and prospective analysis of 185 cancer patients admitted to the ICU at Guy's Hospital (259 admissions), a large tertiary referral oncology centre between February 2004 and July 2008. RESULTS: One hundred and fifteen patients had haematological malignancies of whom 30.4% died in ICU. Seventy patients had solid tumours. ICU mortality was 27.1%. Fifty-four patients had >1 admission to ICU. ICU survivors had significantly lower acute physiology and chronic health evaluation II scores and less failed organ systems on admission to ICU and less organ failure during stay in the ICU. Neutropenia, sepsis and re-admission were not associated with an increased mortality. Six-month mortality rates for patients with haematological malignancies and solid tumours were 73 and 78.6%, respectively. CONCLUSION: Short-term outcome of critically ill cancer patients in ICU is better than previously reported. The decision to admit cancer patients to ICU should depend on the severity of the acute illness rather than factors related to the malignancy. In appropriate patients, invasive organ support and re-admission should not be withheld.

Cardiac arrests in hemodialysis patients: An ongoing challenge.

Hemodialysis patients have significant cardiac-related mortality. Sudden cardiac arrests in the dialysis unit are infrequent events but carry a poor prognosis. The predominant rhythm is ventricular tachycardia/fibrillation. Although the exact etiologies are not clear, several studies have confirmed an increased incidence on the first day after the weekend interval. Use of cardioprotective drugs and possibly an implantable cardioverter defibrillator may improve the prognosis of survivors after a cardiac arrest. More research is needed in this field.