Waking Up in Pain: a prospective unselected cohort study of pain in 3702 patients immediately after surgery in the Danish Realm.

BACKGROUND: Acute and persistent pain after surgery is well described. However, no large-scale studies on immediate postoperative pain in the operating room (OR) exist, hindering potential areas of research to improve clinical outcomes. Thus, we aimed to describe the occurrence and severity of immediate postoperative pain in a large, unselected cohort. METHODS: This was a prospective cohort study, encompassing all procedures in 31 public hospitals in the Danish Realm, during a 5-day period including the weekend. Data on procedures and anesthesia were collected and the main outcome was occurrence of moderate or severe pain in the OR. Secondary outcomes included pain, sedation and nausea in the OR or during the first 15 min in the postanesthesia care unit (PACU) including relevant risk factors. Descriptive and logistic regression statistics were used. RESULTS: A total of 3675 procedures were included for analysis (87% inclusion rate). Moderate or severe pain occurred in 7.4% (95% CI 6.5% to 8.3%) of cases in the OR immediately after awakening, rising to 20.2% in the OR and/or PACU. Large intraprocedure and interprocedure variations occurred (0.0%-37.5%), and in 20% of cases with epidural-general anesthesia patients experienced moderate or severe pain. Independent risk factors were female sex, younger age, preoperative pain, daily opioid use and major surgical procedures. CONCLUSION: Moderate or severe pain in the immediate postoperative phase occurred in 20% of all cases with procedure and anesthesiological technique variations, suggesting a need for identification of relevant procedure-specific risk factors and development of preventive treatments. TRIAL REGISTRATION NUMBER: RoPR ID 43191.

Enhancing Predicted Efficacy of Tumor Treating Fields Therapy of Glioblastoma Using Targeted Surgical Craniectomy: A Computer Modeling Study.

OBJECTIVE: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. METHODS: We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic clinical scenarios. RESULTS: For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60-70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30-50%. The observed effects were highly focal and targeted at the regions of pathology underlying the craniectomy. No significant changes were observed in surrounding healthy tissues. Median field strengths in tumor tissue increased with increasing craniectomy diameter up to 50-70 mm. Multiple smaller burr holes were more efficient than single craniectomies of equivalent area. Craniectomy caused no significant field enhancement in the deeply seated tumor, but rather a focal enhancement in the brain tissue underlying the skull defect. CONCLUSIONS: Our results provide theoretical evidence that small and clinically feasible craniectomies may provide significant enhancement of TTFields intensity in cerebral hemispheric tumors without severely compromising brain protection or causing unacceptable heating in healthy tissues. A clinical trial is being planned to validate safety and efficacy.