Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects.

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.

Increasing Use of Prophylactic Open Abdomen Therapy With Vacuum Assisted Wound Closure and Mesh Mediated Fascial Traction After Repair of Ruptured Abdominal Aortic Aneurysm.

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.

A window of opportunity for ICU end-of-life care-A retrospective multicenter cohort study.

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.

Frailty and health-related life quality in long-term follow up of intensive care patients above 65 years old: Protocol for a Norwegian prospective, observational multicenter study.

BACKGROUND: Frailty is strongly correlated with mortality in intensive care unit patients, yet routine screening among intensive care patients is rarely performed. The aim of this study is to assess frailty and health-related quality of life (HRQoL) in patients before intensive care admission and to compare this with outcomes after 3 and 12-months. The Clinical Frailty Scale and EQ-5D-5L will be used to assess frailty and HRQoL, respectively. METHODS: This is an ongoing, prospective observational study including patients from five Norwegian ICU's. Inclusion criteria are patients aged ≥65 years requiring invasive mechanical ventilation for ≥24 h. The Clinical Frailty Scale and EQ-5D-5L are administered at baseline (before critical illness) and at 3- and 12-months post-inclusion. Additional data collected includes patient characteristics, ICU treatment details, illness severity and mortality. The EQ-5D-5L will be compared to Norwegian population norms and assessed for measurement properties. RESULTS: Inclusion started July 2022 and will be stopped at 350 patients. The study will be completed in 2025. CONCLUSION: The study will assess the feasibility and measurement properties of the Clinical Frailty Scale and EQ-5D-5L in ICU survivors by telephone at long-term follow-up study and will give additional information on the frailty and HRQoL of intensive care survivors. CLINICAL TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov NCT06012942. Protocol version 2.7.1, 19.05.2023.

Platelet transfusions in adult ICU patients with thrombocytopenia: A sub-study of the PLOT-ICU inception cohort study.

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.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

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.

Zopiclone versus placebo for short-term treatment of insomnia in patients with advanced cancer-a double-blind, randomized placebo-controlled clinical multicenter phase IV trial.

PURPOSE: Insomnia is frequent in patients with advanced cancer, and a variety of pharmacological agents is used to treat this condition. Still, few clinical trials have investigated the effectiveness of pharmacological sleep therapies in this patient group. We aimed to study the short-term effectiveness of zopiclone on sleep quality in patients with advanced cancer who report insomnia. METHODS: A randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase IV clinical trial in adult patients with metastatic malignant disease and insomnia. Patients were treated with zopiclone or placebo for six subsequent nights. Primary end point was patient-reported sleep quality during the final study night (NRS 0-10). Secondary end points were patient-reported sleep onset latency (SOL) and total sleep time (TST). RESULTS: Forty-one patients were randomized, with 18 being analyzed in the zopiclone group and 21 in the placebo group. Median age was 66, median Karnofsky performance score was 80, and 56% were male. Mean sleep quality at end of study was 2.9 (CI 2.3 to 3.8) in the zopiclone group and 4.5 (CI 3.6 to 5.4) in the placebo group (p = 0.021). At end of study, SOL was significantly different between the treatment groups: zopiclone 29 min (CI 13 to 51) and placebo 62 min (CI 40 to 87) (p = 0.045). TST was not significantly different across groups: zopiclone 449 min (403 to 496) and placebo 411 min (CI 380 to 440) (p = 0.167). CONCLUSION: Zopiclone improved short-term patient-reported sleep quality in this cohort of patients with advanced cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02807922.

Acute kidney injury in intensive care patients: Incidence, time course, and risk factors.

BACKGROUND: Acute kidney injury (AKI) is frequent and influences the prognosis of intensive care unit (ICU) patients. The aim of this study was to estimate the incidence, time-course, risk factors, and mortality of AKI among unselected ICU patients. METHODS: All adult ICU patients admitted to the ICU at the University Hospital in Central Norway from 2010 to 2015 with a stay of 24 h or more were included in the study. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. All patients were followed with respect to reversal of AKI. Risk factors for AKI were analyzed using Cox regression. RESULTS: Among 2325 ICU patients, 1245 developed AKI during the ICU stay, corresponding to an incidence of 53.5 % (CI, 51.5-55.5). The incidence according to KDIGO AKI stages 1, 2, and 3 was 26.2, 11.7, and 15.7%, respectively. The median duration of AKI was 24 (CI 19-24), 32 (CI 26-39), and 101 (CI 75-164) hours for AKI KDIGO stage 1, 2, and 3, respectively. AKI was transient, persistent, or AKD in 73.4, 16.5, and 10.0% of the patients with a known outcome. AKI reversal was observed in 72.9% of all AKI patients. Independent risk factors for AKI in a multivariate analysis were hypertension, diabetes, heart disease, and higher body weight. Episodes of mean arterial pressure below 73 mmHg were associated with a higher risk of AKI. CONCLUSIONS: In our material, the incidence of AKI was comparable to what has been reported previously. Risk factors for the development of AKI were a MAP below 73, hypertension, diabetes, heart disease, chronic kidney disease, and higher body weight. Most AKI patients regain their kidney function during the ICU stay, particularly in the KDIGO AKI stages 1 and 2.

The short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer in a randomized, placebo-controlled, double-blind trial.

PURPOSE: Although corticosteroids are frequently used in patients with advanced cancer, few studies have examined the impact of these drugs on patient-reported sleep. We aimed to examine the short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer. METHODS: Patient-reported sleep was a predefined secondary outcome in a prospective, randomized, placebo-controlled, double-blind trial that evaluated the analgesic efficacy of corticosteroids in advanced cancer patients (18+), using opioids, and having pain ≥ 4 past 24 h (NRS 0-10). Patients were randomized to the methylprednisolone group with methylprednisolone 16 mg × 2/day or placebo for 7 days. The EORTC QLQ-C30 (0-100) and the Pittsburgh Sleep Quality Index questionnaire (PSQI) (0-21) were used to assess the impact of corticosteroids on sleep at baseline and at day 7. RESULTS: Fifty patients were randomized of which 25 were analyzed in the intervention group and 22 in the control group. Mean age was 64 years, mean Karnofsky performance status was 67 (SD 13.3), 51% were female, and the mean oral daily morphine equivalent dose was 223 mg (SD 222.77). Mean QLQ-C30 sleep score at baseline was 29.0 (SD 36.7) in the methylprednisolone group and 24.2 (SD 27.6) in the placebo group. At day 7, there was no difference between the groups on QLQ-C30 sleep score (methylprednisolone 20.3 (SD 32.9); placebo 28.8 (SD 33.0), p = 0.173). PSQI showed similar results. CONCLUSIONS: Methylprednisolone 16 mg twice daily for 7 days had no impact on patient-reported sleep in this cohort of patients with advanced cancer. TRIAL REGISTRATION: Clinical trial information NCT00676936 (13.05.2008).

Interventions and symptom relief in hospital palliative cancer care: results from a prospective longitudinal study.

PURPOSE: To study the use of interventions and symptom relief for adult patients with incurable cancer admitted to an acute palliative care unit providing integrated oncology and palliative care services. METHODS: All admissions during 1 year were assessed. The use of interventions was evaluated for all hospitalizations. Patients with assessments for worst and average pain intensity, tiredness, drowsiness, nausea, appetite, dyspnea, depression, anxiety, well-being, constipation, and sleep were evaluated for symptom development during hospitalization. Descriptive statistics was applied for the use of interventions and the paired sample t-test to compare symptom intensities (SIs). RESULTS: For 451 admissions, mean hospital length of stay was 7.0 days and mean patient age 69 years. More than one-third received systemic cancer therapy. Diagnostic imaging was performed in 66% of the hospitalizations, intravenous rehydration in 45%, 37% received antibiotics, and 39% were attended by the multidisciplinary team. At admission and at discharge, respectively, 55% and 44% received oral opioids and 27% and 45% subcutaneous opioids. For the majority, opioid dose was adjusted during hospitalization. Symptom registrations were available for 180 patients. Tiredness yielded the highest mean SI score (5.6, NRS 0-10) at admission and nausea the lowest (2.2). Significant reductions during hospitalization were reported for all assessed SIs (p ≤ 0.01). Patients receiving systemic cancer therapy reported symptom relief similar to those not on systemic cancer therapy. CONCLUSION: Clinical practice and symptom relief during hospitalization were described. Symptom improvements were similar for oncological and palliative care patients.

Desflurane consumption with automated vapour control systems in two different anaesthesia machines. A randomized controlled study.

BACKGROUND: In general anaesthesia practice a fresh gas flow (FGF) of ≥0.5 L/min is usually applied. Automated gas delivery devices are developed to reduce volatile anaesthetic consumption by limiting gas flow. This study aimed to compare desflurane consumption between automated gas control devices compared to conventional low flow anaesthesia in the Flow-I and Aisys anaesthesia machines, and to compare desflurane consumption between the two automated gas delivery devices. We hypothesised that desflurane consumption would be lower with automated gas delivery compared to conventional low flow anaesthesia, and that desflurane consumption could differ between the different gas delivery devices. METHODS: We allocated 160 patients undergoing robot-assisted laparoscopic surgery into four groups, Flow-I with automated gas control, Flow-i with conventional low-flow (1 L/min), Aisys with end tidal gas control and Aisys with conventional low flow. Patients were maintained at minimum alveolar concentration (MAC) 0.7-0.8. Desflurane consumption was recorded after 9, 30 and 60 minutes of anaesthesia. RESULTS: After 60 minutes, compared to conventional low flow anaesthesia, automated gas delivery systems reduced desflurane consumption from 25.8 to 15.2 mL for the Aisys machine (P < .001) and from 22.1 to 16.8 mL for the Flow-I (P < .001). Time to MAC 0.7 and stable FGF was shorter with Aisys endtidal control compared to Flow-I automated gas control. CONCLUSION: Under clinical conditions, we found a reduction in desflurane consumption when using automated gas delivery devices compared to conventional low flow anaesthesia. Both devices were reliable in use.

Frailty and survival in elderly intensive care patients in Norway.

BACKGROUND: Today, 10%-15% of Norwegian intensive care patients are ≥80 years. This proportion will increase significantly over the next 20 years, but it is unlikely that resources for intensive care increase correspondingly. Thus, it is important to establish which patients among elderly people will benefit from intensive care. The main objective of the study was to investigate the relationships between geriatric scoring tools and 30-day mortality. METHODS: The study included 451 Norwegian patients ≥80 years who were included in two prospective European observation studies (VIP (very old intensive care patient)1 of VIP2). Both studies included clinical frailty scale (CFS) while VIP2 also obtained the geriatric scores, comorbidity and polypharmacy score (CPS), Short Form of Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and Katz Activity of Daily Living score (Katz ADL). RESULTS: Survival after 30 days was 59.9%. Risk factors for 30-day mortality were increasing Sequential Organ Failure Assessment (SOFA) score (odds ratio (OR) 1.30; confidence interval (CI) 95% 1.22-1.39) and (CFS) > 3 (CFS 4: OR 1.96 (CI 95% 1.01-3.81); CFS 5-9: OR 1.81 (CI) 95% 1.12-2.93)). Data from VIP2 showed that CFS was the only independent predictor of 30-day mortality when these scores were tested in multivariate analyses separately together with age, SOFA, and gender (OR 1.21 (95% CI 1.03-1.41)). CONCLUSIONS: Elderly intensive care patients had a 30-day survival rate of 59.9%. Factors strongly associated with 30-day mortality were increasing SOFA score and increasing frailty (CFS). Other geriatric scores had no significant association with survival in multivariate analyses.

Circulatory trajectories after out-of-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Circulatory failure frequently occurs after out-of-hospital cardiac arrest (OHCA) and is part of post-cardiac arrest syndrome (PCAS). The aim of this study was to investigate circulatory disturbances in PCAS by assessing the circulatory trajectory during treatment in the intensive care unit (ICU). METHODS: This was a prospective single-center observational cohort study of patients after OHCA. Circulation was continuously and invasively monitored from the time of admission through the following five days. Every hour, patients were classified into one of three predefined circulatory states, yielding a longitudinal sequence of states for each patient. We used sequence analysis to describe the overall circulatory development and to identify clusters of patients with similar circulatory trajectories. We used ordered logistic regression to identify predictors for cluster membership. RESULTS: Among 71 patients admitted to the ICU after OHCA during the study period, 50 were included in the study. The overall circulatory development after OHCA was two-phased. Low cardiac output (CO) and high systemic vascular resistance (SVR) characterized the initial phase, whereas high CO and low SVR characterized the later phase. Most patients were stabilized with respect to circulatory state within 72 h after cardiac arrest. We identified four clusters of circulatory trajectories. Initial shockable cardiac rhythm was associated with a favorable circulatory trajectory, whereas low base excess at admission was associated with an unfavorable circulatory trajectory. CONCLUSION: Circulatory failure after OHCA exhibits time-dependent characteristics. We identified four distinct circulatory trajectories and their characteristics. These findings may guide clinical support for circulatory failure after OHCA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061.

Changes in peripheral arterial blood pressure after resuscitative endovascular balloon occlusion of the aorta (REBOA) in non-traumatic cardiac arrest patients.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) may be an adjunct treatment to cardiopulmonary resuscitation (CPR). Aortic occlusion may increase aortic pressure and increase the coronary perfusion pressure and the cerebral blood flow. Peripheral arterial blood pressure is often measured during or after CPR, however, changes in peripheral blood pressure after aortic occlusion is insufficiently described. This study aimed to assess changes in peripheral arterial blood pressure after REBOA in patients with out of hospital cardiac arrest. METHODS: A prospective observational study performed at the helicopter emergency medical service in Trondheim (Norway). Eligible patients received REBOA as adjunct treatment to advanced cardiac life support. Peripheral invasive arterial blood pressure and end-tidal CO2 (EtCO2) was measured before and after aortic occlusion. Differences in arterial blood pressures and EtCO2 before and after occlusion was analysed with Wilcoxon Signed Rank test. RESULTS: Five patients were included to the study. The median REBOA procedural time was 11 min and median time from dispatch to aortic occlusion was 50 min. Two patients achieved return of spontaneous circulation. EtCO2 increased significantly 60 s after occlusion, by a mean of 1.16 kPa (p = 0.043). Before occlusion the arterial pressure in the compression phase were 43.2 (range 12-112) mmHg, the mean pressure 18.6 (range 4-27) mmHg and pressure in the relaxation phase 7.8 (range - 7 - 22) mmHg. After aortic occlusion the corresponding pressures were 114.8 (range 23-241) mmHg, 44.6 (range 15-87) mmHg and 14.8 (range 0-29) mmHg. The arterial pressures were significant different in the compression phase and as mean pressure (p = 0.043 and p = 0.043, respectively) and not significant in the relaxation phase (p = 0.223). CONCLUSION: This study is, to our knowledge, the first to assess the peripheral invasive arterial blood pressure response to aortic occlusion during CPR in the pre-hospital setting. REBOA application during CPR is associated with a significantly increase in peripheral artery pressures. This likely indicates improved central aortic blood pressure and warrants studies with simultaneous peripheral and central blood pressure measurement during aortic occlusion. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov ( NCT03534011 ).

Improper monitoring and deviations from physiologic treatment goals in patients with brain injury in the early phases of emergency care.

Severe traumatic brain injury (TBI), out-of-hospital cardiac arrest (OHCA) and intracerebral- and subarachnoid hemorrhage (ICH/SAH) are conditions associated with high mortality and morbidity. The aim of this study was to investigate the feasibility of obtaining continuous physiologic data and to identify possible harmful physiological deviations in these patients, in the early phases of emergency care. Patients with ICH/SAH, OHCA and severe TBI treated by the Physician-staffed Emergency Medical Service (P-EMS) between September and December 2016 were included. Physiological data were obtained from site of injury/illness, during transport, in the emergency department (ED) and until 3 h after admittance to the intensive care unit. Physiological deviations were based on predefined target values within each 5-min interval. 13 patients were included in the study, of which 38% survived. All patients experienced one or more episodes of hypoxia, 38% experienced episodes of hypercapnia and 46% experienced episodes of hypotension. The mean proportion of time without any monitoring in the pre-hospital phase was 29%, 47% and 56% for SpO2, end-tidal CO2 and systolic blood pressure, respectively. For the ED these proportions were 57%, 71% and 56%, respectively. Continuous physiological data was not possible to obtain in this study of critically ill and injured patients with brain injury. The patients had frequent deviations in blood pressure, SpO2 and end tidal CO2-levels, and measurements were frequently missing. There is a potential for improved monitoring as a tool for quality improvement in pre-hospital critical care.

An in-hospital clinical care pathway with integrated decision support for cancer pain management reduced pain intensity and needs for hospital stay.

PURPOSE: A clinical care pathway for pain management in a palliative care unit was studied with outcomes related to patients, physicians, and health care service. Mandatory use of patient-reported outcome measures (PROMs) and physician-directed decision support (DS) were integrated parts of the pathway. METHODS: Adult cancer patients with pain intensity (PI) ≥ 5 (NRS 0-10) at admission were eligible. The patients reported average and worst PI at admission, day four, and discharge. The physicians completed the DS at admission and day four. The DS presented potential needs for treatment changes based on pain severity and pathophysiology. The physicians reported treatment changes due to input from the DS system. The two primary outcomes were average and worst PI changes from admission to discharge. Hospital length of stay (LOS) was registered. RESULTS: Of 52 included patients, 41 were discharged alive. For those, the mean average PI at admission and at discharge was 5.8 and 2.4, respectively, a reduction of 3.4 points (CI 95% 2.7-4.1). The corresponding worst pain intensities were 7.9 and 3.8, a reduction of 4.1 points (CI 95% 3.4-4.8). The physicians completed DS forms for all patients. Fifty-five percent (CI 95% 41-69) of the patients had pain intervention changes based on the DS. A significant reduction in LOS (4.4 days, CI 95% 0.5-8.3) was observed during the study period. CONCLUSIONS: The interventions were implemented according to the intentions and PI was reduced as hypothesized. For evaluation of generalizability, the interventions should be studied in other settings and with a controlled design.

Sleep quality in hospitalized patients with advanced cancer: an observational study using self-reports of sleep and actigraphy.

PURPOSE: Although patients with advanced cancer report poor sleep quality, few studies have assessed sleep quality with a combination of subjective and objective measures. We aimed to examine sleep quality in hospitalized patients with advanced cancer by combining patient-reported outcome-measures (PROMs) and polysomnography (PSG) or actigraphy. METHODS: A one-night prospective observational study of sleep in hospitalized patients with metastatic cancer using WHO step III opioids was conducted. Total sleep time, sleep onset latency, number of awakenings, and wake after sleep onset were assessed by PROMs and actigraphy. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) (range; 0-21), where higher scores indicate worse sleep quality. RESULTS: Forty patients were monitored. Median age was 70, median oral morphine equivalent dose was 80 mg/24 h (10-1725), median Karnofsky Performance Score was 50 (20-90), and median time to death from inclusion was 38 days (4-319). Mean PSQI score was 6.5 (SD ± 3.4). PROMs and actigraphy of mean (SD) sleep onset latency were 46 (± 64) and 35 min (± 61), respectively, while mean time awake at night was 37 (± 35) and 40 min (± 21). PROMs and actigraphy differed on number of awakenings (mean 2 (± 1) vs. 24 (± 15), p Ë‚ 0.001). Bland-Altman plots showed large individual differences between PROMs and actigraphy. PSG was not feasible. CONCLUSIONS: PROMs and actigraphy documented poor sleep quality, but a lack of agreement across methods. The study demonstrates a need to improve assessment of sleep quality and treatment of sleep disturbance in hospitalized patients with advanced cancer near end of life.

Pain management index (PMI)-does it reflect cancer patients' wish for focus on pain?

BACKGROUND: The pain management index (PMI) was developed to combine information about the prescribed analgesics and the self-reported pain intensity in order to assess physicians' response to patients' pain. However, PMI has been used to explore undertreatment of cancer pain. The present study explores prevalence of negative PMI and its associations to clinical variables, including the patient-perceived wish for more attention to pain. METHODS: A single-center, cross-sectional, observational study of cancer patients was conducted. Data on demographics and clinical variables, as well as patient-perceived wish for more attention to pain, were registered. PMI was calculated. Negative PMI indicates that the analgesics prescribed might not be appropriate to the pain intensity reported by the patient, and associations to negative PMI were explored by logistic regression models. RESULTS: One hundred eighty-seven patients were included, 53% had a negative PMI score. Negative PMI scores were more frequent among patients with breast cancer (OR 4.2, 95% CI 1.3, 13.5), in a follow-up setting (OR 12.1, 95% CI 1.4, 101.4), and were inversely associated to low performance status (OR 0.14, 95% CI 0.03, 0.65). Twenty-two percent of patients with negative PMI scores reported that they wanted more focus on pain management, versus 13% among patients with a non-negative PMI score; the difference was not statistically significant. CONCLUSION: A high prevalence of negative PMI was observed, but only 1/5 of patients with a negative PMI wanted more attention to pain by their physician. Our findings challenge the use of PMI as a measure of undertreatment of cancer pain.

Continuous subcutaneous infusion for pain control in dying patients: experiences from a tertiary palliative care center.

BACKGROUND: Continuous subcutaneous infusion (CSCI) via ambulatory infusion pump (AIP) is a valuable method of pain control in palliative care. When using CSCI, low-dose methadone as add-on to other opioids might be an option in complex pain situations. This study aimed to investigate the effects, and adverse effects, of CSCI for pain control in dying patients, with particular interest in methadone use. METHODS: This was an observational cohort study. Imminently dying patients with pain, admitted to specialized palliative inpatient wards and introduced on CSCI, were monitored daily by staff for symptoms (Integrated Palliative Care Outcome Scale - IPOS), sedation (Richmond Agitation and Sedation Scale - RASS), performance status (Eastern Cooperative Oncology Group - ECOG) and delirium (Confusion Assessment Method - CAM). RESULTS: Ninety-three patients with a median survival of 4 days were included. Of the 47 patients who survived ≥3 days, the proportion of patients with severe/overwhelming pain decreased from 45 to 19% (p < 0.001) after starting CSCI, with only a moderate increase in morphine equivalent daily dose of opioids (MEDD). Alertness was marginally decreased (1 point on the 10-point RASS scale, p = 0.001), whereas performance status and prevalence of delirium, regardless of age, remained unchanged. Both patients with methadone as add-on (MET, n = 13) and patients with only other opioids (NMET, n = 34), improved in pain control (p < 0.05 and 0.001, respectively), despite that MET patients had higher pain scores at baseline (p < 0.05) and were on a higher MEDD (240 mg vs.133 mg). No serious adverse effects demanding treatment stop were reported. CONCLUSIONS: CSCI via AIP is an effective way to reduce pain in dying patients without increased adverse effects. Add-on methadone may be beneficial in patients with severe complex pain.

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.