Asger Granfeldt

Background: Pain is common in intensive care unit (ICU) patients with up to one‐third experiencing pain at rest and even more during mobilization and clinical procedures. This survey aimed to explore physicians' attitudes and preferences regarding pain management in adult ICU patients in the Nordic countries. Methods: We conducted an electronic survey targeting physicians working regularly in an ICU in the Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. The survey focused on pain assessment, pharmacological treatments, and post‐discharge follow‐up of adult ICU patients. Results: The survey was distributed to 606 physicians, and 360 responses were received (overall response rate 59%). Respondents were primarily from Denmark, with only a few respondents from the remaining Nordic countries. Most respondents were specialists in anesthesiology working in mixed ICUs in public specialist hospitals. Standardized pain assessment tools were widely used in non‐sedated patients, while only half of respondents employed standardized pain assessment tools in sedated patients. Respondents reported that pain was assessed multiple times daily in both non‐sedated and sedated patients. Daily wake‐up calls in sedated patients were considered important by almost all respondents. Morphine was the preferred opioid for oral‐ and intravenous bolus administration, while remifentanil was preferred for intravenous continuous administration. However, preferences varied across countries with regard to both opioid‐ and non‐opioid analgesics. Nearly half of respondents expressed concerns regarding the development of opioid‐induced hyperalgesia. Methadone was the most frequently preferred drug for opioid weaning, although preferences varied between countries. Most respondents acknowledged the importance of ICU‐follow up programs, but only about half of respondents reported that their ICU currently offered a follow‐up service. Conclusion: This Nordic survey explored ICU physicians' attitudes and preferences regarding pain management in adult ICU patients. Respondents reported assessing pain frequently, employing standardized pain assessment tools primarily in non‐sedated patients. Daily wake‐up calls in sedated patients were generally perceived as important. Interestingly, preferences regarding opioid‐ and non‐opioid analgesics varied between Nordic countries. ICU‐follow up programs were recognized as important but were not consistently implemented. Despite a high overall response rate, the generalizability of our findings is impaired by limited participation in most Nordic countries except Denmark. Editorial Comment: This survey describes the physician perspective on predominantly pharmacological pain management in selected ICUs within the Nordic countries.

Background: Disrupted cerebral blood flow is suggested to contribute to secondary brain injury after cardiac arrest (CA). This study aimed to investigate cerebral microcirculation after return of spontaneous circulation (ROSC) following asphyxial CA. We hypothesized that contraction of pericytes after ROSC compromises cerebral capillary blood flow. Methods: Transgenic C57BL/6NRj mice (n=19) of both sexes were studied. Mice were expressing tdTomato as a fluorescent reporter under the control of the platelet‐derived growth factor receptor β promoter to label pericytes. Chronic cranial windows were implanted 3 weeks before the experiment. Four minutes of asphyxial CA was followed by cardiopulmonary resuscitation. Two‐photon microscopy assessed cerebral hemodynamics in the same cohort of mice at both 3 and 24 hours after ROSC. Results: Of 13 mice in the CA group, 9 achieved ROSC; 6 and 5 mice survived to 3 and 24 hours after ROSC, respectively. Arterial blood pressure was similar between groups 3 and 24 hours after ROSC. At 3 hours after ROSC, pial arteries and penetrating arterioles were constricted in the CA group compared with sham (arteriole diameter, 12.2 μm [95% CI, 10.9–13.4] versus 15.6 μm [95% CI, 13.8–17.5] in CA and sham; P =0.003). Similarly, first‐ and second‐ to third‐order capillaries showed reduced diameters 3 hours after ROSC (first‐order diameter, 3.9 μm [95% CI, 3.5–4.2] versus 5.3 μm [95% CI, 4.8–5.9] in CA and sham; P =0.002). The vasoconstriction was associated with slower red blood cell velocities throughout the capillary network (for second‐ to third‐order capillaries upstream from venule; 0.78 mm/s [95% CI, 0.46–1.09] versus 2.14 mm/s [95% CI, 1.73–2.55]; P <0.001) and increased capillary flow stalling. Artery‐to‐vein mean transit time was increased and relative transit‐time heterogeneity was decreased 3 hours after ROSC. By 24 hours after ROSC, vessel diameters, blood flow velocity, transit time, and capillary stalling were not different compared with sham. Conclusions: Cerebrovascular vasospasm 3 hours after ROSC was associated with impaired cerebral microcirculation and increased capillary flow stalling.

Cerebral autoregulation is impaired in the postcardiac arrest period, potentially altering cerebral blood flow and exacerbating neurological injury after resuscitation. To our knowledge, the current study is the first to demonstrate that cerebral arteries exhibit reduced myogenic response, tone, and contractility in an animal model following resuscitation from cardiac arrest. These alterations in vasoreactivity appear to result, at least in part, from decreased calcium sensitivity in cerebral vascular smooth muscle cells.

Right ventricular (RV) function assessment using catheter‐derived pressure‐volume (PV) loops is used in translational research, providing detailed insights into cardiac mechanics. Its practical implementation requires methodological accuracy to ensure rigor, reproducibility and transparency. However, current practices for PV loop acquisition are set at individual laboratories, resulting in overall practice remaining largely unknown. This study aimed to explore current practices in RV PV loop acquisition in large animal research. We therefore conducted a scoping review registered on the Open Science Framework and guided by PRISMA Extension for Scoping Reviews, with comprehensive searches in PubMed, Embase, Scopus, and Web of Science (December 2024). Eligible studies included large animal models published after 2014 using conductance or admittance catheters. Out of 5133 identified records, 62 met inclusion criteria. The review revealed underreporting and substantial variability in methodology, particularly in catheter placement, calibration, and ventilatory mode during PV loop recording. Catheter insertion sites included RV inflow (42%) and outflow tracts (19.4%); fluoroscopy was used in 51.6%. Calibration was not reported in one‐third of studies. Loop recording during apnea were reported in 23%, mechanical ventilation in 26%, and was not specified in 51%. Overall, RV PV loop protocols show substantial heterogeneity, highlighting the need for standardized methodological reporting, to improve transparency, research reproducibility and translational significance. Expert consensus is warranted to establish methodological guidelines.

Midazolam is a commonly used sedative for patients on extracorporeal membrane oxygenation (ECMO). However, its long context-sensitive half-life is of concern. Remimazolam may be a suitable alternative. This study compares the sequestration of remimazolam and midazolam in an in-vitro ECMO circuit. Sixteen in-vitro ECMO circuits were prepared with either Ringer lactate or a combination of red blood cells and fresh frozen plasma. Each circuit operated at a flow of 3 L/min at 37°C for 24 hours. Remimazolam (1 mg) or midazolam (1 mg) was injected, creating four experimental groups. Blood samples for measurement of drug concentrations were collected at predefined time points. The percentage of drug remaining at 24 hours was comparable for remimazolam and midazolam (mean [standard deviation {SD}]: 3.7% [0.9] and 2.9% [0.5]) in Ringer lactate–perfused circuits and higher for midazolam compared with remimazolam (mean [SD] 52% [13] and 15% [2]) in blood-perfused circuits. The concentration of the remimazolam metabolite CNS7054 increased from 29 (8) ng/ml at 5 minutes to 173 (31) ng/ml at 24 hours. Drug sequestration of remimazolam in in-vitro ECMO circuit is comparable to midazolam in circuits perfused with Ringer lactate. In circuits perfused with blood, the percentage of drug remaining at 24 hours is lower for remimazolam.