Management of adult patients with haematological malignancies in critical care.

There are a diverse range of haematological malignancies with varying clinical presentations and prognoses. Patients with haematological malignancy may require admission to critical care at the time of diagnosis or due to treatment related effects and complications. Although the prognosis for such patients requiring critical care has improved, there remain uncertainties in optimal clinical management. Identification of patients who will benefit from critical care admission is challenging and selective involvement of palliative care may help to reduce unnecessary and non-beneficial treatments. While patients with haematological malignancy can present a challenge to critical care physicians, good outcomes can be achieved. In this narrative review, we provide a brief overview of relevant haematological malignancies for the critical care physician and a summary of recent treatment advances. Subsequently, we focus on critical care management for the patient with haematological malignancy including sepsis; acute respiratory failure; prevention and treatment of tumour lysis syndrome; thrombocytopaenia; and venous thromboembolism. We also discuss immunotherapeutic-specific related complications and their management, including cytokine release syndrome and immune effector cell associated neurotoxicity syndrome associated with chimeric antigen receptor T-cell therapy. While the management of haematological malignancies is highly specialised and increasingly centralised, acutely unwell patients often present to their local hospital with complications requiring critical care expertise. The aim of this review is to provide a contemporary overview of disease and management principles for non-specialist critical care teams.

Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic.

BACKGROUND: Cancer diagnostics and surgery have been disrupted by the response of health care services to the coronavirus disease 2019 (COVID-19) pandemic. Progression of cancers during delay will impact on patients' long-term survival. PATIENTS AND METHODS: We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of 3 and 6 months and periods of disruption of 1 and 2 years. Using health care resource costing, we contextualise attributable lives saved and life-years gained (LYGs) from cancer surgery to equivalent volumes of COVID-19 hospitalisations. RESULTS: Per year, 94 912 resections for major cancers result in 80 406 long-term survivors and 1 717 051 LYGs. Per-patient delay of 3/6 months would cause attributable death of 4755/10 760 of these individuals with loss of 92 214/208 275 life-years, respectively. For cancer surgery, average LYGs per patient are 18.1 under standard conditions and 17.1/15.9 with a delay of 3/6 months (an average loss of 0.97/2.19 LYGs per patient), respectively. Taking into account health care resource units (HCRUs), surgery results on average per patient in 2.25 resource-adjusted life-years gained (RALYGs) under standard conditions and 2.12/1.97 RALYGs following delay of 3/6 months. For 94 912 hospital COVID-19 admissions, there are 482 022 LYGs requiring 1 052 949 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.08 LYG and 0.46 RALYGs. CONCLUSIONS: Modest delays in surgery for cancer incur significant impact on survival. Delay of 3/6 months in surgery for incident cancers would mitigate 19%/43% of LYGs, respectively, by hospitalisation of an equivalent volume of admissions for community-acquired COVID-19. This rises to 26%/59%, respectively, when considering RALYGs. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued.

Nonsteroidal anti-inflammatory drugs and pain in cancer patients: a systematic review and reappraisal of the evidence.

BACKGROUND: Emerging data highlights the potential role of cyclooxygenase (COX) inhibitors in the primary prevention of malignancy, reducing metastatic spread and improving overall mortality. Despite nonsteroidal anti-inflammatory drugs (NSAIDs) forming a key component of the WHO analgesic ladder, their use in cancer pain management remains relatively low. This review re-appraises the current evidence regarding the efficacy of COX inhibitors as analgesics in cancer pain, providing a succinct resource to aid clinicians' decision making when determining treatment strategies. METHODS: Medline® and Embase® databases were searched for publications up to November 2018. Randomised controlled trials (RCTs) and double-blind controlled studies considering the use of NSAIDs for management of cancer-related pain in adults were included. Animal studies, case reports, and retrospective observational data were excluded. RESULTS: Thirty studies investigating the use of NSAIDs in cancer pain management were identified. There is a lack of high-quality evidence regarding the analgesic efficacy of NSAIDs in cancer pain, with short study durations and heterogeneity in outcome measures limiting the ability to draw meaningful conclusions. CONCLUSIONS: Despite the renewed interest in these cost-effective, well-established medications in cancer treatment outcomes, there is a paucity of data from the past 15 yr regarding their efficacy in cancer pain management. However, when analgesic strategies in the cancer population are being formulated, it is important that the potential benefits of this class of drug are considered. Further work investigating the role of NSAIDs in cancer pain management is undoubtedly warranted.

Incidence of postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis.

BACKGROUND: Trials suggest that the use of i.v. hydroxyethyl starch (HES) solutions is associ-ated with increased risk of death and acute kidney injury (AKI) in critically ill patients. It is uncertain whether similar adverse effects occur in surgical patients. METHODS: Systematic review and meta-analysis of trials in which patients were randomly allocated to 6% HES solutions or alternative i.v. fluids in patients undergoing surgery. Ovid Medline, Embase, Cinhal, and Cochrane Database of Systematic Reviews were searched for trials comparing 6% HES with clinically relevant non-starch comparator. The primary end-point was hospital mortality. Secondary endpoints were requirement for renal replacement therapy (RRT) and author-defined AKI. Pre-defined subgroups were cardiac and non-cardiac surgery. RESULTS: Four hundred and fifty-six papers were identified; of which 19 met the inclusion criteria. In total, 1567 patients were included in the analysis. Dichotomous outcomes were expressed as a difference of proportions [risk difference (RD)]. There was no difference in hospital mortality [RD 0.00, 95% confidence interval (CI) -0.02, 0.02], requirement for RRT (RD -0.01, 95% CI -0.04, 0.02), or AKI (RD 0.02, 95% CI -0.02 to 0.06) between compared arms overall or in predefined subgroups. CONCLUSIONS: We did not identify any differences in the incidence of death or AKI in surgical patients receiving 6% HES. Included studies were small with low event rates and low risk of heterogeneity. Narrow CIs suggest that these findings are valid. Given the absence of demonstrable benefit, we are unable to recommend the use of 6% HES solution in surgical patients.

Comparison of the prognostic accuracy of scoring systems, cardiopulmonary exercise testing, and plasma biomarkers: a single-centre observational pilot study.

BACKGROUND: Current approaches to risk assessment before major surgery have important limitations. The aim of this pilot study was to compare predictive accuracy of preoperative scoring systems, plasma biomarkers, and cardiopulmonary exercise testing (CPET) for complications after major non-cardiac surgery. METHODS: Single-centre, observational study of patients aged ≥40 yr undergoing major elective non-cardiac surgery. Before surgery, risk scores were calculated and blood samples collected for measurement of plasma biomarkers. Patients underwent CPET for measurement of anaerobic threshold (AT) and peak oxygen consumption ( peak). After surgery, patients were followed for 28 days to evaluate complications and major adverse cardiac events (MACE). Data are presented as area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals. RESULTS: A total of 100 patients were recruited between April 2009 and October 2010; 17 of whom did not proceed to surgery. CPET variables suggested good predictive accuracy for MACE [AT: AUROC 0.83 (0.69-0.96); peak AUROC 0.81 (0.69-0.96)] and poor predictive accuracy for all complications [AT: AUROC 0.64 (0.52-0.77); peak AUROC 0.64 (0.52-0.77)]. There was a trend towards predictive accuracy of the plasma biomarkers B-type natriuretic peptide and estimated glomerular filtration rate (calculated from serum creatinine) for MACE but not all complications. C-reactive protein, ASA score, and revised cardiac risk index had little or no predictive value. CONCLUSIONS: These pilot data suggest that CPET and plasma biomarkers may improve risk assessment before surgery. Only large clinical studies can confirm this observation and define the optimal use of these tests in clinical practice.

Neutrophil gelatinase-associated lipocalin and albuminuria as predictors of acute kidney injury in patients treated with goal-directed haemodynamic therapy after major abdominal surgery.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a new biomarker for the early identification of acute kidney injury (AKI). There is also increasing evidence of an association between urinary albumin/creatinine ratio (ACR) and AKI. The primary aim of this study was to evaluate the clinical utility of these biomarkers to predict AKI in a population of perioperative patients treated with goal-directed haemodynamic therapy (GDHT). Secondary aims were to examine NGAL and ACR as sensitive biomarkers to detect the effects of GDHT and to investigate the association of these biomarkers with secondary outcomes. METHODS: Urine was obtained from 109 patients admitted to a critical care unit following major abdominal surgery. Patients were treated with intravenous fluid, GDHT with intravenous fluid or GDHT with intravenous fluid and dopexamine. Urine was collected preoperatively, and at times 0, 8 and 24 h postoperatively and outcome monitored for 28 days. RESULTS: There were no significant differences in NGAL or ACR concentrations between the cohorts treated with GDHT compared to standard care. However, both biomarker concentrations rose significantly in all cohorts over the time points. There were no significant differences in NGAL observed between patients who developed AKI and those who did not. However, there were significantly higher ACR preoperatively in patients who developed AKI. There were higher NGAL concentrations in patients who developed an infection and who died. CONCLUSIONS: NGAL has a poor predictive role in evaluating AKI in this clinical setting. Preoperative ACR may have a role as an AKI marker.

Mortality and utilisation of critical care resources amongst high-risk surgical patients in a large NHS trust.

Previous reports describe a population of non-cardiac surgical patients at high risk of complications and death. Outcomes are sub-optimal for such patients, perhaps in part related to inadequate provision or ineffective utilisation of critical care resources. In this study, data describing 26,051 in-patient non-cardiac surgical procedures performed in a large NHS Trust between April 2002 and March 2005 were extracted from local databases. Of these procedures, 2 414 (9.3%) were high risk with an overall mortality rate of 12.2% and a prolonged hospital stay (high-risk population median (IQR) 16 (9-30) days vs standard risk 3 (2-6) days). Mortality rates for specific procedures were consistent with UK averages. However, only 852 (35.3%) high-risk patients were admitted to a critical care unit at any stage after surgery. Of 294 high-risk patients who died, only 144 (49.0%) were admitted to a critical care unit at any time and only 75 (25.6%) of these deaths occurred within a critical care area. Mortality rates were high amongst patients discharged and readmitted to critical care (37.7%) and amongst those admitted to critical care following initial postoperative care on a standard ward (29.9%). These data suggest that the outcome of high-risk general surgical patients could be improved by adequate provision and more effective utilisation of critical care resources.

Cardiac output monitoring: basic science and clinical application.

Derangements in the circulation are a common feature of sepsis, trauma, major surgery and other critical illnesses. Detailed evaluation of the circulation is therefore an essential aspect of the clinical management of such patients. The use of cardiac output monitoring technology is an increasingly important aspect of evaluating patients in the operating theatre, critical care unit and elsewhere. There are now a number of different technologies available for this purpose, which use a diverse range of physiological principles. A detailed understanding of the physiological principles applied by such technology is essential for safe and effective use in clinical practice. The aim of this article is to describe the physiological principles used to measure cardiac output and their application in various monitors in common clinical use.