ABSTRACT
BACKGROUND: The "window of opportunity" for intensive care staff to deliver end-of-life (EOL) care lies in the timeframe from "documenting the diagnosis of dying" to death. Diagnosing the dying can be a challenging task in the ICU. We aimed to describe the trajectories for dying patients in Danish intensive care units (ICUs) and to examine whether physicians document that patients are dying in time to perform EOL care and, if so, when a window of opportunity for EOL care exists. METHODS: From the Danish Intensive Care Database, we identified patients ≥18 years old admitted to Danish ICUs between January and December 2020 with an ICU stay of >96 h (four days) and who died during the ICU stay or within 7 days after ICU discharge. A chart review was performed on 250 consecutive patients admitted from January 1, 2020, to ICUs in the Central Denmark Region. RESULTS: In most charts (223 [89%]), it was documented that the patient was dying. Of those patients who received mechanical ventilation, 171 (68%) died after abrupt discontinuation of mechanical ventilation, and 63 (25%) died after gradual withdrawal. Patients whose mechanical ventilation was discontinued abruptly died after a median of 1 h (interquartile range [IQR]: 0-15) and 5 h (IQR: 2-15) after a diagnosis of dying was recorded. In contrast, patients with a gradual withdrawal died after a median of 108 h (IQR: 71-189) and 22 h (IQR: 5-67) after a diagnosis of dying was recorded. CONCLUSIONS: EOL care hinges on the ability to diagnose the dying. This study shows that there is a window of opportunity for EOL care, particularly for patients who are weaned from mechanical ventilation. This highlights the importance of intensifying efforts to address EOL care requirements for ICU patients and those discharged from ICUs who are not eligible for readmission.
ABSTRACT
OBJECTIVES: Nutrition impact symptoms (NIS) are associated with weight loss (WL), and decreased energy intake in cross-sectional studies. We aimed to ascertain associations between changes in NIS burden, energy intake and WL over time in patients with advanced cancer. METHODS: Adult patients from an observational radiotherapy study for painful bone metastases self-reported NIS and WL using the Patient-Generated Subjective Global Assessment tool (PG-SGA) at baseline and week eight (W8). NIS burden, the sum of NIS per patient, categorised as 0, 1-2 and ≥3 with changes defined as 2-point differences from baseline to W8 were used. Energy intake was assessed by 24-hour recall interviews. RESULTS: 111 patients (72.1%) were analysed and grouped by NIS burden; 0 NIS (44.1%), 1-2 NIS (30.6%) and ≥3 NIS (25.2%). Patients with NIS burden of ≥3 reported higher baseline WL compared with those with 1-2 or 0 NIS (46.4% vs 18.2% vs 10.2%, respectively, p=0.002). At W8, 21 patients (19%) reported improved NIS burden, accompanied by a lower proportion of severe (≥5%) new-onset WL (19% vs 42.1%) and higher energy intake (median 29.6 vs 21.2 kcal/kg) than those with worsened NIS burden (17.1%). CONCLUSIONS: NIS management may improve energy intake and prevent WL, emphasising the importance of systematic follow-up and interventions. CLINICALTRIALSGOV REGISTRATION: NCT02107664.
ABSTRACT
BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 109/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 1011 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 1011 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 109/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.
ABSTRACT
The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) µM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.
Subject(s)
Analgesics, Opioid , Cancer Pain , Delayed-Action Preparations , Morphine , Pharmacogenetics , Humans , Morphine/adverse effects , Morphine/pharmacokinetics , Morphine/administration & dosage , Male , Female , Cancer Pain/drug therapy , Cancer Pain/genetics , Middle Aged , Analgesics, Opioid/pharmacokinetics , Analgesics, Opioid/adverse effects , Analgesics, Opioid/administration & dosage , Delayed-Action Preparations/pharmacokinetics , Aged , Pharmacogenetics/methods , Polymorphism, Single Nucleotide/genetics , Morphine Derivatives/pharmacokinetics , Morphine Derivatives/adverse effects , Adult , Pharmacogenomic Variants , Toll-Like Receptor 2/geneticsABSTRACT
PURPOSE: The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning (ML) model with explainable artificial intelligence to predict 1-year survival after palliative radiotherapy (RT) for bone metastasis. MATERIALS AND METHODS: Data collected in the multicentric PRAIS trial were extracted for 574 eligible adults diagnosed with metastatic cancer. The primary end point was the overall survival (OS) at 1 year (1-year OS) after the start of RT. Candidate covariate predictors consisted of 13 clinical and tumor-related pre-RT patient characteristics, seven dosimetric and treatment-related variables, and 45 pre-RT laboratory variables. ML models were developed and internally validated using the Python package. The effectiveness of each model was evaluated in terms of discrimination. A Shapley Additive Explanations (SHAP) explainability analysis to infer the global and local feature importance and to understand the reasons for correct and misclassified predictions was performed. RESULTS: The best-performing model for the classification of 1-year OS was the extreme gradient boosting algorithm, with AUC and F1-score values equal to 0.805 and 0.802, respectively. The SHAP technique revealed that higher chance of 1-year survival is associated with low values of interleukin-8, higher values of hemoglobin and lymphocyte count, and the nonuse of steroids. CONCLUSION: An explainable ML approach can provide a reliable prediction of 1-year survival after RT in patients with advanced cancer. The implementation of SHAP analysis provides an intelligible explanation of individualized risk prediction, enabling oncologists to identify the best strategy for patient stratification and treatment selection.
Subject(s)
Bone Neoplasms , Machine Learning , Palliative Care , Humans , Bone Neoplasms/secondary , Bone Neoplasms/radiotherapy , Bone Neoplasms/mortality , Palliative Care/methods , Male , Female , Prognosis , Aged , Middle Aged , AlgorithmsABSTRACT
OBJECTIVE: Open abdomen therapy (OAT) is commonly used to prevent or treat abdominal compartment syndrome (ACS) in patients with ruptured abdominal aortic aneurysms (rAAAs). This study aimed to evaluate the incidence, treatment, and outcomes of OAT after rAAA from 2006 to 2021. Investigating data on resuscitation fluid, weight gain, and cumulative fluid balance could provide a more systematic approach to determining the timing of safe abdominal closure. METHODS: This was a single centre observational cohort study. The study included all patients treated for rAAA followed by OAT from October 2006 to December 2021. RESULTS: Seventy-two of the 244 patients who underwent surgery for rAAA received OAT. The mean age was 72 ± 7.85 years, and most were male (n = 61, 85%). The most frequent comorbidities were cardiac disease (n = 31, 43%) and hypertension (n = 31, 43%). Fifty-two patients (72%) received prophylactic OAT, and 20 received OAT for ACS (28%). There was a 25% mortality rate in the prophylactic OAT group compared with the 50% mortality in those who received OAT for ACS (p = .042). The 58 (81%) patients who survived until closure had a median of 12 (interquartile range [IQR] 9, 16.5) days of OAT and 5 (IQR 4, 7) dressing changes. There was one case of colocutaneous fistula and two cases of graft infection. All 58 patients underwent successful abdominal closure, with 55 (95%) undergoing delayed primary closure. In hospital survival was 85%. Treatment trends over time showed the increased use of prophylactic OAT (p ≤ .001) and fewer ACS cases (p = .03) assessed by Fisher's exact test. In multivariable regression analysis fluid overload and weight reduction predicted 26% of variability in time to closure. CONCLUSION: Prophylactic OAT after rAAA can be performed safely, with a high rate of delayed primary closure even after long term treatment.
Subject(s)
Aortic Aneurysm, Abdominal , Aortic Rupture , Intra-Abdominal Hypertension , Negative-Pressure Wound Therapy , Surgical Mesh , Humans , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/mortality , Male , Aged , Female , Negative-Pressure Wound Therapy/adverse effects , Aortic Rupture/surgery , Aortic Rupture/mortality , Intra-Abdominal Hypertension/etiology , Intra-Abdominal Hypertension/prevention & control , Intra-Abdominal Hypertension/surgery , Aged, 80 and over , Treatment Outcome , Retrospective Studies , Traction/adverse effects , Traction/methods , Time Factors , Middle Aged , Open Abdomen Techniques/adverse effects , Risk Factors , Abdominal Wound Closure Techniques/adverse effects , Abdominal Wound Closure Techniques/instrumentation , Fasciotomy/adverse effects , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Complications/epidemiologyABSTRACT
Background: Ischaemic intestines could be a driver of critical illness through an inflammatory response. We have previously published reports on a biomarker for intestinal injury, plasma Intestinal Fatty Acid Binding Protein (IFABP), and inflammatory biomarkers after out-of-hospital cardiac arrest (OHCA). In this post-hoc study we explored the potential indirect effects of intestinal injury mediated through the inflammatory response on organ dysfunction and mortality. Methods: We measured IFABP and twenty-one inflammatory biomarkers in 50 patients at admission to intensive care unit after OHCA. First, we stratified patients on median IFABP and compared biomarkers between "low" and "high" IFABP. Second, by causal mediation analysis, we assessed effects of IFABP through the two most important inflammatory biomarkers, interleukin (IL)-6 and terminal complement complex (TCC), on day two circulatory variables, Sequential Organ Failure Assessment (SOFA)-score, and 30-day mortality. Results: Cytokines and complement activation were higher in the high IFABP group. In mediation analysis, patients on the 75th percentile of IFABP, compared to the 25th percentile, had 53% (95% CI, 33-74; p < 0.001) higher risk of dying, where 13 (95% CI, 3-23; p = 0.01) percentage points were mediated through an indirect effect of IL-6. Similarly, the indirect effect of IFABP through IL-6 on SOFA-score was significant, but smaller than potential other effects. Effects through IL-6 on circulatory variables, and all effects through TCC, were not statistically significant and/or small. Conclusion: Effects of intestinal injury mediated through inflammation on organ dysfunction and mortality were limited. Small, but significant, effects through IL-6 were noted.Trial registration: ClinicalTrials.gov: NCT02648061.
ABSTRACT
Background: Opioid switching is common, however, conversion tables have limitations. Guidelines suggest postswitch dose reduction, yet, observations show opioid doses may increase postswitch. Objectives: To document the opioid conversion factor postswitch in cancer, and whether pain and adverse effect outcomes differ between switched opioid groups. Design/Setting: This multicenter prospective longitudinal study included people with advanced cancer in Australia. Clinical data (demographics, opioids) and validated instruments (pain, adverse effects) were collected twice, seven days apart. Results: Opioid switch resulted in dose increase (median oral morphine equivalent daily dose 90 mg [interquartile range {IQR} 45-184] to 150 mg [IQR 79-270]), reduced average pain (5.1 [standard deviation {SD} 1.7] to 3.8 [SD 1.6]), and reduced adverse effects. Hydromorphone dose increased 2.5 times (IQR 1.0-3.6) above the original conversion factor used. Conclusions: Opioid switching resulted in overall dose increase, particularly when switching to hydromorphone. Higher preswitch dosing may require higher dose conversion ratios. Dose reduction postswitch risks undertreatment and may not be always appropriate.
Subject(s)
Cancer Pain , Chronic Pain , Neoplasms , Humans , Analgesics, Opioid , Hydromorphone/adverse effects , Cancer Pain/drug therapy , Prospective Studies , Longitudinal Studies , Chronic Pain/drug therapy , Neoplasms/drug therapyABSTRACT
INTRODUCTION: The documentation on patient reported outcomes the first weeks at home following total hip arthroplasty (THA) is sparse. Length of hospital stay after THA is substantially reduced. Therefore, knowledge on whether patients are managing their own postoperative rehabilitation early after discharge is important, in order to give the patients realistic preoperative information, to modify expectations and enable patients to monitor their own rehabilitation process. METHODS: Eighty-two THA patients were included in a prospective cohort study. Patient-reported outcomes were collected twice a week thirty days postoperatively using a web-based registration tool. Numeric rating scales (0-10) for pain, function, and quality of life, EQ-5D, and the use of opioids were registered. Four weeks postoperatively a telephone interview were conducted. Pain, EQ5D and hip specific physical function score (HOOS-PS) were recorded preoperatively, at three- and twelve-months follow-up. RESULTS: Pain was maintained the first days after hospital discharge. From day 0 to day 30, pain decreased from 4.0 (SD 2.23) to 2.3 (SD 1.75), function improved from 4.4 (SD 2.06) to 7 (SD 1.57), quality of life improved from 6.3 (SD 2.69) to 7.8 (SD 1.47), and EQ-5D improved from 0.4 to (SD 0.27) to 0.7 (SD 0.14). After 30 days, 32% still used opioids. All patients completed the web-registration. Pain, EQ-5D and HOOS-PS improved substantially from preoperatively to twelve months follow-up. CONCLUSION: Fast-track THA patients can expect continued postoperative pain and impaired quality of life the first week at home, before gradually improvement. After thirty days, 32 % of the patients still used opioids.
Subject(s)
Arthroplasty, Replacement, Hip , Humans , Follow-Up Studies , Prospective Studies , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/rehabilitation , Quality of Life , Pain, Postoperative/drug therapy , Patient Reported Outcome Measures , Internet , Treatment OutcomeSubject(s)
Breakthrough Pain , Neoplasms , Humans , Analgesics, Opioid/therapeutic use , Pain/drug therapy , FentanylABSTRACT
Cancer pain intensity (PI) fluctuates, but the relationship between pain flares and background pain with respect to pain management is not settled. We studied how flare and background PIs corresponded with treatment results for background cancer pain. Patients admitted to an acute palliative care unit with average and/or worst PI ≥ 1 on the 11-point numeric rating scale were included. Average and worst PI at admission and average PI at discharge were collected. We examined how the difference and ratio between worst and average PI and average PI at admission, were associated with average PI development during hospitalization. Positive differences between worst and average PI at admission were defined as pain flares. Ninety out of 131 patients had pain flares. The reduction in average PI for patients with flares was 0.9 and for those without, 1.9 (p = 0.02). Patients with large worst minus average PI differences reported the least improvement, as did those with large worst/average PI ratios. Patients with pain flares and average PI ≤ 4 at admission had unchanged average PI during hospitalization, while those with pain flares and average PI > 4 experienced pain reduction (2.1, p < 0.001). Large pain flares, in absolute values and compared to background PI, were associated with inferior pain relief.
Subject(s)
Cancer Pain , Neoplasms , Humans , Palliative Care/methods , Cancer Pain/therapy , Pain/etiology , Neoplasms/complications , Neoplasms/therapy , Pain Management/methodsABSTRACT
Aim: Associations between gene variants and opioid net effect are unclear. We conducted an exploratory pharmacogenetic analysis of 35 gene variants and opioid response in advanced cancer. Patients & methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects) and DNA (blood). Negative binomial regression and logistic regression were used. Results: Within 54 participants, eight statistically significant associations (p = 0.002-0.038) were observed between gene variants and opioid dose, pain scores or adverse effects, the majority being within the neuroimmune TLR4 pathway (IL1B [rs1143634], IL2 [rs2069762], IL6 [rs1800795], BDNF [rs6265]) and ARRB2 pathway (ARRB2 [rs3786047], DRD2 [rs6275]). Conclusion: Neuroimmune pathway genes may contribute to differences in opioid response in cancer and may be included in future similar studies.
ABSTRACT
PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
Subject(s)
Platelet Transfusion , Thrombocytopenia , Adult , Humans , Male , Female , Middle Aged , Platelet Transfusion/adverse effects , Cohort Studies , Prospective Studies , Thrombocytopenia/epidemiology , Thrombocytopenia/etiology , Intensive Care Units , Hemorrhage/etiology , Retrospective StudiesABSTRACT
BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
Subject(s)
Respiratory Insufficiency , Adult , Humans , Respiratory Insufficiency/therapy , Respiration, Artificial , Lung , Intensive Care Units , RespirationABSTRACT
Opioid switching is a common practice of substituting one opioid for another to improve analgesia or adverse effects; however, it has limited evidence. This study aimed to examine the effectiveness of opioid switching in advanced cancer. This multi-center prospective cohort study recruited patients assessed to switch opioids (opioid switch group) or to continue ongoing opioid treatment (control group). Clinical data (demographics, opioids) and validated instruments (pain and adverse effects) were collected over two timepoints seven days apart. Descriptive analyses were utilized. Non-parametric tests were used to determine differences. Fifty-four participants were recruited (23 control group, 31 switch group). At the follow-up, opioid switching reduced pain (worst, average, and now) (p < 0.05), uncontrolled breakthrough pain (3-fold reduction, p = 0.008), and psychological distress (48% to 16%, p < 0.005). The switch group had a ≥25% reduction in the reported frequency of seven moderate-to-severe adverse effects (score ≥ 4), compared to a reduction in only one adverse effect in the control group. The control group experienced no significant pain differences at the follow-up. Opioid switching is effective at reducing pain, adverse effects, and psychological distress in a population with advanced cancer pain, to levels of satisfactory symptom control in most patients within 1 week.
ABSTRACT
INTRODUCTION: Dexmedetomidine, an alpha-2 adrenergic receptor agonist with potential opioid sparing properties, is utilized in palliative medicine, but the knowledge base for this practice is limited. We describe concomitant use of dexmedetomidine and opioids in an acute palliative care unit. METHODS: We included all hospitalized palliative cancer care patients treated with dexmedetomidine from January 2019 to January 2021. Demographics, opioid doses, dexmedetomidine indications and dosing, reported effects and adverse responses, as well as treatment lengths were recorded. RESULTS: Three women and six men aged 42-66 years with metastatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status I-IV used dexmedetomidine and opioids concomitantly. Indications for dexmedetomidine were pain (n = 7) and anxiety (n = 2). Dexmedetomidine was administered intravenously in two patients and subcutaneously in seven. All administrations were continuous infusions; initial doses ranged from 240 to 1344 µg/24 h with later doses from 240 to 2440 µg/24 h. Physicians reported relief from pain and anxiety, but two patients required neuraxial pain management during admission. At day 2 of dexmedetomidine treatment, the opioid dose was reduced in six out of nine patients. For all patients with available data at day 7, mean opioid dose was reduced to 74% of the initial dose. When excluding the two patients requiring neuraxial pain management, the corresponding number was 80%. Two patients had transient hypotension, but dexmedetomidine was well tolerated and in no cases withdrawn due to adverse effects. Mean dexmedetomidine treatment length was 40 days. CONCLUSIONS: Dexmedetomidine treatment decreased opioid consumption and was well tolerated in a retrospective study of nine palliative cancer care patients. It may represent a treatment option late in the disease trajectory.
ABSTRACT
BACKGROUND: The impact of intestinal injury in cardiac arrest is not established. The first aim of this study was to assess associations between clinical characteristics in out-of-hospital cardiac arrest (OHCA) and a biomarker for intestinal injury, Intestinal Fatty Acid Binding Protein (IFABP). The second aim was to assess associations between IFABP and multiple organ dysfunction and 30-day mortality. METHODS: We measured plasma IFABP in 50 patients at admission to intensive care unit (ICU) after OHCA. Demographic and clinical variables were analysed by stratifying patients on median IFABP, and by linear regression. We compared Sequential Organ Failure Assessment (SOFA) score, haemodynamic variables, and clinical-chemistry tests at day two between the "high" and "low" IFABP groups. Logistic regression was applied to assess factors associated with 30-day mortality. RESULTS: Several markers of whole body ischaemia correlated with intestinal injury. Duration of arrest and lactate serum concentrations contributed to elevated IFABP in a multivariable model (p < 0.01 and p = 0.04, respectively). At day two, all seven patients who had died were in the "high" IFABP group, and all six patients who had been transferred to ward were in the "low" group. Of patients still treated in the ICU, the "high" group had higher total, renal and respiratory SOFA score (p < 0.01) and included all patients receiving inotropic drugs. IFABP predicted mortality (OR 16.9 per standard deviation increase, p = 0.04). CONCLUSION: Cardiac arrest duration and lactate serum concentrations were risk factors for intestinal injury. High levels of IFABP at admission were associated with multiple organ dysfunction and mortality. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061.
Subject(s)
Intestines , Out-of-Hospital Cardiac Arrest , Humans , Intestines/injuries , Prospective Studies , Multiple Organ Failure/etiology , Biomarkers , Organ Dysfunction Scores , Out-of-Hospital Cardiac Arrest/complications , Lactates , Intensive Care UnitsABSTRACT
Purpose: Individual genetic variation can affect both pain expression and opioid response. Large cohort datasets are required to validate evidence influencing genomic factors in opioid response. This study examined the feasibility of establishing an opioid pharmacogenomics registry for cancer patients containing longitudinal matched clinical, symptom, pharmacological, and genomic data, with an a priori feasibility target of 50 participants within 12 months. Methods: Consecutive patients with advanced cancer receiving opioids across five palliative care services were recruited. Clinical data (demographics, pain data, adverse effects, medications) and blood (DNA, RNA, pharmacokinetics) were collected over two time points. Patient and clinician qualitative interviews were conducted to assess acceptability. This study was approved by the SVHA Ethics Committee, Melbourne, Australia (HREC 252/18). Results: Enrollment for the registry was deemed feasible. Fifty-eight participants were recruited (median age 63.7, 45% female, 83% complete data), with the most frequent diagnosis being lung cancer (n = 18, 33%) and oxycodone the most frequently prescribed opioid (n = 30, 52%). Qualitative data indicated positive engagement from both patients and clinicians. Conclusion: Establishing a longitudinal opioid pharmacogenomic registry in patients with cancer receiving palliative care is feasible and readily acceptable.