BACKGROUND:Patients with cancer account for 15% of all admissions to critical care and so an understanding of the pathophysiology and anticipated complications of specialist treatment is essential for the intensive care clinician. The development of chimeric antigen receptor T-cell therapy for haematological malignancies and immune checkpoint inhibitors for solid organ tumours has led to significant improvements in the prognosis of those patients whose tumours respond. This review is intended to provide the non-specialist with an understanding of the current concepts in pathophysiology, diagnosis and management of complications due to chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors for malignant disease. METHODS:We performed searches of electronic databases to identify relevant peer-reviewed publications in the literature. Basic science; clinical trials; cohort studies; systematic reviews; meta-analyses; and guidelines were eligible for inclusion. Abstracts were screened to identify publications relevant to immune effector cell toxicities of chimeric antigen receptor T-cell therapy and immune-related adverse events of immune checkpoint inhibitors. RESULTS:While the pathophysiology for toxicities due to chimeric antigen receptor T-cells and immune checkpoint inhibitors remains incompletely understood, targeted drug therapies have been successfully implemented for toxicities such as cytokine release syndrome. Corticosteroids remain an important component of pharmacological management. The diagnosis of toxicities remains largely clinical, and a high index of suspicion should remain for infective complications. Management of toxicities should be undertaken in conjunction with the patient's primary oncologist. CONCLUSION:Despite significant advances in the development of targeted immunotherapy, the mechanism of action for the resultant toxicities remains poorly understood and limits the development of predictive models, diagnostic biomarkers and highly effective treatment options. Further research is needed to identify treatment regimens which minimise the use of corticosteroids in chimeric antigen receptor T-cell and immune checkpoint inhibitor-associated toxicities.

We conducted a feasibility randomized controlled trial exploring the effect of aromatherapy massage on sleep in critically ill patients. Patients were randomized to receive aromatherapy massage or usual care, and feasibility of recruitment and outcome data completion was captured. Sleep (depth) was assessed through Bispectral Index monitoring and self/nurse-reported Richards-Campbell Sleep Questionnaires, and the Sleep in the ICU Questionnaire. Thirty-four patients participated: 17 were randomized to aromatherapy massage and 17 to control. Five participants who received the intervention completed outcomes for analysis (alongside eight controls). A larger study was deemed unfeasible in this population, highlighting the value of testing feasibility of complex interventions, such as massage for sleep in ICU.

The rapid development of novel therapies which simultaneously offer hope in the most challenging cases but which often come with a raft of potential toxicities, some of which we are yet to fully elucidate, presents a new frontier in critical care. This chapter summarizes the current state of the art in the intensive care management of patients who have been treated with targeted therapies that modulate the immune system and discusses the implications for the development of support systems in the future.

6586 Background: Sepsis is a life threatening organ dysfunction caused by a dysregulated host response to infection. Patients with cancer are at high risk of developing sepsis and requiring admission to the intensive care unit (ICU). Patients with cancer and sepsis have been found to have worse survival than non-cancer patients, with 90 day survival for cancer patients ranging from 28% to 72%. Survival differs between studies due to multiple factors including variably mixed haemato-oncology and solid tumor cohorts and varying definitions of sepsis. Our objectives were to accurately assess short, medium and long term survival of patients admitted to ICU with a solid tumor and sepsis and to identify the best predictors of 90 day survival at admission. Methods: We conducted a retrospective cohort survival analysis. We identified adults (aged 18 years and over) admitted to ICU with sepsis and a solid tumor between 1 st January 2011 and 31 st December 2020 at a tertiary oncology center with hospitals at two sites (London and Surrey, United Kingdom). We defined sepsis using the Sepsis-3 definition. The primary outcome was 90 day survival, but we also calculated 30 day, 180 day, 1 year and 5 year survival. Survival was calculated excluding patients lost to follow up. Univariate and multivariate analyses were undertaken to identify factors that differed between survivors and non-survivors at day 90. We used the parametric accelerated failure time model for multivariate analysis to generate time ratios (TR). Results: 625 patients were identified, with 131 patients lost to follow up by 5 years. The median age was 64 years (Interquartile Range 54-71) and 56% were male. 84.8% (530/625) survived to ICU discharge. The 30, 90 and 180 day survival rates were 72% (439/610), 59.5% (353/593) and 51.7% (300/580) respectively. 1 year survival was 38.7% (221/571) and 5 year survival 8.1% (40/494). Multivariate analysis identified the presence of localized (TR 7.85, 95% CI 4.00 -15.41) or regionalized disease (TR 4.71, 95% CI 2.74-8.08) compared to distant metastatic disease, surgery on the day of admission (TR 6.78, 95% CI 3.24-14.19), lactate (TR 0.80, 95% CI 0.74-0.87), SOFA score (TR 0.84, 95% CI 0.79-0.89), previous radiotherapy (TR 0.53, 95% CI 0.32-0.88), previous medical cancer treatment (TR 0.67, 95% CI 0.42-1.07), bacteremia (TR 2.14, 95% CI 1.25-3.64) and albumin (TR 1.06, 95% CI 1.02-1.10) as independent predictors of 90 day survival. Conclusions: This study of solid tumor patients admitted to ICU is one of the largest to date with the longest follow up period, providing up to date survival data to inform clinicians and patients. Patients with solid tumors and sepsis admitted to ICU have short and medium term survival rates comparable to non-cancer populations and therefore the presence of cancer should not prevent ICU admission. Prior oncological therapies may affect survival in patients admitted to ICU with sepsis.

The intensive care units in North West London are part of one of the oldest critical carenetworks in the UK, forming a mature and established strategic alliance to shareresources, experience and knowledge for the benefit of its patients. North WestLondon saw an early surge in COVID-19 admissions, which urgently threatened thecapacity of some of its intensive care units even before the UK government announcedlockdown. The pre-existing relationships and culture within the network allowed itsmembers to unite and work rapidly to develop agile and innovative solutions, protectingany individual unit from becoming overwhelmed, and ultimately protecting its patients.Within a short 50-day period 223 patients were transferred within the network todistribute pressures. This unprecedented number of critical care transfers, combinedwith the creation of extra capacity and new pathways, allowed the region to continue tooffer timely and unrationed access to critical care for all patients who would benefitfrom admission. This extraordinary response is a testament to the power and benefitsof a regionally networked approach to critical care, and the lessons learned maybenefit other healthcare providers, managers and policy makers, especially in regionscurrently facing new outbreaks of COVID-19.

ABSTRACT The Intensive Care Society (ICS) has recently published guidance on the transfer of critically ill adults. Since 2007, the North West London Critical Care Network has documented and audited patient transfers undertaken across 13 hospitals, and trained staff in transferring critically ill or injured patients. In 2015/16 the network introduced intra-hospital transfer documentation and applied the same transfer training and audit methodology for critically ill patients being moved within hospitals. While increasing data capture and with a targeted training strategy adapted from transfer experience, the network has seen a reduction in number and severity of incidents in the region. In contrast to this experience, no formalised processes exists to support the inter-hospital or intra-hospital transfer of patients from enhanced care areas or wards not embedded within critical care. Often very little data is collected from these areas, but we suspect transfer risks are higher in these cases as a consequence of the deficit of structured transfers. In collaboration with members of the critical care network, we have developed a basic training module along with the use of a transfer form which has been well received and had a positive impact in terms of incidents reported.

To summarize the most recent available clinical and pre-clinical research data concerning the effects of propofol-based total intravenous anesthesia (TIVA) and volatile anesthesia on oncological outcomes and to discuss the biological basis by which these drugs are purported to exert effects on the cancer cell and on the host.

The MDT approach to high-risk and major cancer surgery should adopt a holistic approach to the care and treatment of the patient in question. Instead of adopting a binary mindset, where a patient is declared ‘fit’ or ‘not fit’ for surgery, the MDT approach should be the centrepoint for the personalized care of each individual patient considered for surgery.

Editor—We read with interest the article by Whiteman and colleagues.1Whiteman AR Dhesi JK Walker D The high-risk surgical patient: a role for a multi-disciplinary team approach?.Br J Anaesth. 2016; 116: 311-314Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Surgical resection still forms the mainstay of treatment for many patients with cancer. It is estimated that by 2020 that a significant proportion of all health care spending in more developed countries will be associated with cancer surgery.2Short MN Aloia TA Ho V The influence of complications on the costs of complex cancer surgery.Cancer. 2014; 120: 1035-1041Crossref PubMed Scopus (48) Google Scholar This in part reflects the fact patients being considered for cancer surgery are becoming older, frailer and more co-morbid. Patient characteristic data (Table 1) of all patients having elective major open abdominal and pelvic cancer surgery over a four year period at our institution support this statement. Therefore having a robust decision making process for those considered for cancer surgery, is vital to ensure patients have both the best outcome (s) and health care resources are used appropriately. In their editorial Whiteman and colleagues1Whiteman AR Dhesi JK Walker D The high-risk surgical patient: a role for a multi-disciplinary team approach?.Br J Anaesth. 2016; 116: 311-314Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar highlight the role of a multi-disciplinary team (MDT) approach in decision making for high-risk surgical patients. We would like to raise a few points with regards to the high- risk MDT with patient's presenting for major cancer surgery with reference to our institutional experience:Table 1Patients presenting for open major abdominal and pelvic surgery at The Royal Marsden NHS Foundation Trust over a four year period2011-20122012-20132013-20142014-2015P-valuesn = 348n =318n = 341n = 281Age (yr)65 [62–68]67 [60–71]67 [58–74]71 [62–78]<0.01$$POSSUM physiology score20 [14–30]26 [26– 34]27 [21–38]29 [18 – 40]<0.01$$WHO performance status1 [0–4]1[0–4]1 [0–4]2[0–4]0.04$$BMI (kg/m2)24.5 (4.6)25.6 (4.1)25.9 (4.8)26.8 (5.6)0.02?Karnofsky Score80 [30–100]80 [30–100]80 [30–100]70 [20–100]<0.01$$metastatic disease present32 (9.2%)37 (11.6%)42 (12.3%)68 (24.2%)<0.01xCPET variablesn = 208n = 212n = 216n = 143AT (mls/kg/min)10.5 [8.3–11.3]10.3 [8.2–12.4]10 [8.6–12.7]9.4 [8.0– 13.2]<0.01$$VO2 peak (mls/kg/min)14.8 [12.3–17.2]14.6 [11.8–18.2]14.3 [11.3– 17.3]13.8 [11.3–16.9]<0.01$$VE/VCO2 at AT34.3 [30.0–39.2]34.5 [27.6–37.8]36.5 [27.3–39.8]38.4 [30.5–41.2]<.0.01$$Test used $$Kruskal-Wallis Analysis of Variance;? one way analysis of variance (ANOVA); × χ2 test.Data presented as median [IQR] or mean (SD) or % in parentheses; P < 0.05 significant.CPET cardiopulmonary exercise testing; AT anaerobic threshold; VO2 peak oxygen consumption;.VE/VCO2 ventilatory equivalents. Open table in a new tab Test used $$Kruskal-Wallis Analysis of Variance;? one way analysis of variance (ANOVA); × χ2 test. Data presented as median [IQR] or mean (SD) or % in parentheses; P < 0.05 significant. CPET cardiopulmonary exercise testing; AT anaerobic threshold; VO2 peak oxygen consumption;. VE/VCO2 ventilatory equivalents. The term outcome is an important one and should be the focus of any high-risk MDT, especially for cancer surgery. The majority of the data on outcome following surgery exists on mortality and morbidity. As a result of advances in surgical techniques and perioperative technique, mortality and significant morbidity in many high volume cancer centres is low following major cancer.3Jones C Kelliher L Dickinson M et al.Randomized clinical trial on enhanced recovery versus standard care following open liver resection.Br J Surg. 2013; 100: 1015-1024Crossref PubMed Scopus (194) Google Scholar4Schultz NA Larsen PN Klarskov B et al.Evaluation of a fast-track programme for patients undergoing liver resection.Br J Surg. 2013; 100: 138-143Crossref PubMed Scopus (89) Google Scholar In our institution 1253 out of the 1288 (97.3%) of the patients presented in Table 1 who had elective major complex cancer were discharged to their homes. This however does not mean their quality life or disability free living was better post-surgery and we do not have robust data in this area. In fact research into factors that predict quality of life following major oncological surgical specialties is sparse. Future perioperative research needs to focus on these areas as principle outcomes. Patient engagement will be key to the process since quality of life can have significant interindividual variability. The high risk MDT should not be a binary process (i.e. fit or not fit for cancer surgery because quality of life will be poor or mortality high). It should also offer the following:•Identification of the patient that can be optimized before surgery: for example prehabiliation5West MA Loughney L Lythgoe D et al.Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study.Br J Anaesth. 2015; 114: 244-251Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar in cancer surgery has shown promise.•Consideration of the mode of surgery. Robotic surgery for certain procedures for example is being shown to have beneficial outcomes in cancer surgery.6Ind TEJ Marshall C Hacking M et al.Introducing robotic surgery into an endometrial cancer service-a prospective evaluation of clinical and economic outcomes in a UK institution.Int J Med Robot. 2016; 12: 137-144Crossref PubMed Scopus (17) Google Scholar•The timing of the surgery in relation to other treatments such as chemotherapy or radiotherapy that can be influence patient fitness and morbidity.7Bovelli D Plataniotis G Roila F ESMO Guidelines Working Group Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines.Ann Oncol. 2010; 21: v277-v282Abstract Full Text Full Text PDF PubMed Scopus (282) Google Scholar•The institution that will offer the patient the best outcome. High volume cancer centres with protocolised pathways often have better outcomes then lower volume centres.8Ihse I The volume-outcome relationship in cancer surgery: a hard sell.Ann Surg. 2003; 238: 777-781Crossref PubMed Scopus (48) Google Scholar•Consideration of the postoperative recovery. For some high- risk patients, the surgery itself is a prelude to a prolonged and debilitating stay in the intensive care unit, and the impact of this needs to be included in the assessment of outcome.•Consideration of the many alternatives to cancer surgery such as interventional radiological options or gamma knife.9Matsunaga S Shuto T Kawahara N Suenaga J Inomori S Fujino H Gamma Knife surgery for metastatic brain tumors from primary breast cancer: treatment indication based on number of tumors and breast cancer phenotype.J Neurosurg. 2010; 113: 65-72Crossref PubMed Google Scholar•An opportunity for an informed discussion of the risks of surgery supported by evidence, such as the use of risk calculators10Protopapa KL Simpson JC Smith NC Moonesinghe SR Development and validation of the surgical outcome risk tool (SORT)…..J Surg. 2014; 101: 1774-1783Crossref PubMed Scopus (148) Google Scholar or cardiopulmonary exercise testing11Kasivisvanathan R Abbassi-Ghadi N McLeod AD et al.Cardiopulmonary exercise testing for predicting postoperative morbidity in patients undergoing hepatic resection surgery.HPB (Oxford). 2015; 17: 637-643Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholarrather than anecdote. The practicalities of a high-risk MDT in cancer surgery are also important. The ideal format is a one- stop poly-clinic where the patient sees the oncologists, surgeon, anaesthetist, intensivist and any number of other relevant specialists. Not only does this facilitate inter-discipline discussion it also reduces time delays in seeing multiple specialists and enables a definitive treatment plan to be implemented early. Few institutions to our knowledge emulate this model because of the logistics involved. A more feasible option will be a mobile MDT, where a lead person through information technology systems or direct communication facilitates discussion. Ultimately the overall purpose of the high risk MDT in cancer surgery should be to ensure the right patient has the right intervention at the right time resulting in the best possible quality of life. The ′perioperative physician′ or anaesthetist will play an essential role in the future of this process for major cancer surgery. None declared. ReplyBritish Journal of AnaesthesiaVol. 117Issue 5PreviewEditor—We thank for Kasivisvanathan and colleagues for their reply to our editorial.1 We agree that the mainstay of the perioperative MDT (multidisciplinary team) meeting shouldn't just be a decision as to whether or not to operate, but a method of individualising care and streaming patients into the right care pathway for the perioperative period. We read with interest about their experiences of perioperative cancer care at the Royal Marsden Hospital. It was a need for improvement in quality in cancer care that lead to the initial development of the multidisciplinary team meeting2 and it may well be within cancer surgery that we see the development of robust perioperative MDT working. Full-Text PDF Open Archive

Purpose of reviewMost cancer patients experience pain and many will require opioids. However, the effects of opioids on cancer progression, metastasis, and recurrence is increasingly being questioned. There is evidence that opioids affect immune system function, angiogenesis, apoptosis, and invasion in a potentially deleterious manner. This review will examine the preclinical and clinical evidence. Recent findingsRecent clinical data have struggled to find robust evidence that opioids promote cancer progression. Although most study has involved morphine, differential effects of other opioids on immune function and cancer are revealing a more complex picture. SummaryAlthough there is a biologically plausible story, evidence for the action of opioids on cancer is mixed. Indeed, it may even be that in the chronic setting morphine has a beneficial effect on outcome in certain cancer types. This review critically examines and evaluates the evidence for the action of opioids on the processes involved in cancer progression. In the light of the uncertainty of opioid effect on cancer, any decision making should be tempered by knowing that stress and pain undoubtedly contribute to cancer progression.

Purpose of review Most cancer patients experience pain and many will require opioids. However, the effects of opioids on cancer progression, metastasis, and recurrence is increasingly being questioned. There is evidence that opioids affect immune system function, angiogenesis, apoptosis, and invasion in a potentially deleterious manner. This review will examine the preclinical and clinical evidence. Recent findings Recent clinical data have struggled to find robust evidence that opioids promote cancer progression. Although most study has involved morphine, differential effects of other opioids on immune function and cancer are revealing a more complex picture. Summary Although there is a biologically plausible story, evidence for the action of opioids on cancer is mixed. Indeed, it may even be that in the chronic setting morphine has a beneficial effect on outcome in certain cancer types. This review critically examines and evaluates the evidence for the action of opioids on the processes involved in cancer progression. In the light of the uncertainty of opioid effect on cancer, any decision making should be tempered by knowing that stress and pain undoubtedly contribute to cancer progression.

P001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP efflux

Wigmore, Tim BM, BCh, FRCA, MA, FCICM, FFICM; Gottumukkala, Vijaya MB, BS, MD (Anes), FRCA; Riedel, Bernhard MBChB, FCA, FANZCA, FASE, MMed, MBA, PhD Author Information