Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study.

BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. RESULTS: Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4-12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1-5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1-2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3-4]), prone positioning (OR 3 95% CI [1.4-6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7-3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1-6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. CONCLUSIONS: Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.

Local Anesthetics Inhibit the Growth of Human Hepatocellular Carcinoma Cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapeutic options. Retrospective studies have shown that the administration of local anesthetics (LAs) during cancer surgery could reduce cancer recurrence. Besides, experimental studies reported that LAs could inhibit the growth of cancer cells. Thus, the purpose of this study was to investigate the effects of LAs on human HCC cells. METHODS: The effects of 2 LAs (lidocaine and ropivacaine) (10 to 10 M) were studied after an incubation of 48 hours on 2 HCC cell lines, namely HuH7 and HepaRG. Cell viability, cell cycle analysis, and apoptosis and senescence tests were performed together with unsupervised genome-wide expression profiling and quantitative real-time polymerase chain reaction for relevant genes. RESULTS: We showed that LAs decreased viability and proliferation of HuH7 cells (from 92% [P < .001] at 5 × 10 M to 40% [P = .02] at 10 M with ropivacaine and from 87% [P < .001] to 37% [P = .02] with lidocaine) and HepaRG progenitor cells (from 58% at 5 × 10 M [P < .001] to 29% at 10 M [P = .04] with lidocaine and 59% [P < .001] with ropivacaine 5 × 10 M) in concentration-dependent manner. LAs have no effect on well-differentiated HepaRG. Ropivacaine decreased the mRNA level of key cell cycle regulators, namely cyclin A2, cyclin B1, cyclin B2, and cyclin-dependent kinase 1, and the expression of the nuclear marker of cell proliferation MKI67. Lidocaine had no specific effect on cell cycle but increased by 10× the mRNA level of adenomatous polyposis coli (P < .01), which acts as an antagonist of the Wnt/ß-catenin pathway. Both LAs increased apoptosis in Huh7 and HepaRG progenitor cells (P < .01). CONCLUSIONS: The data demonstrate that LAs induced profound modifications in gene expression profiles of tumor cells, including modulations in the expression of cell cycle-related genes that result in a cytostatic effect and induction of apoptosis.

Prevalence and impact of frailty on mortality in elderly ICU patients: a prospective, multicenter, observational study.

PURPOSE: Frailty is a recent concept used for evaluating elderly individuals. Our study determined the prevalence of frailty in intensive care unit (ICU) patients and its impact on the rate of mortality. METHODS: A multicenter, prospective, observational study performed in four ICUs in France included 196 patients aged ≥65 years hospitalized for >24 h during a 6-month study period. Frailty was determined using the frailty phenotype (FP) and the clinical frailty score (CFS). The patients were separated as follows: FP score <3 or ≥3 and CFS <5 or ≥5. RESULTS: Frailty was observed in 41 and 23% of patients on the basis of an FP score ≥3 and a CFS ≥5, respectively. At admission to the ICU, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores did not differ between the frail and nonfrail patients. In the multivariate analysis, the risk factors for ICU mortality were FP score ≥3 [hazard ratio (HR), 3.3; 95% confidence interval (CI), 1.6-6.6; p < 0.001], male gender (HR, 2.4; 95% CI, 1.1-5.3; p = 0.026), cardiac arrest before admission (HR, 2.8; 95% CI, 1.1-7.4; p = 0.036), SAPS II score ≥46 (HR, 2.6; 95% CI, 1.2-5.3; p = 0.011), and brain injury before admission (HR, 3.5; 95% CI, 1.6-7.7; p = 0.002). The risk factors for 6-month mortality were a CFS ≥5 (HR, 2.4; 95% CI, 1.49-3.87; p < 0.001) and a SOFA score ≥7 (HR, 2.2; 95% CI, 1.35-3.64; p = 0.002). An increased CFS was associated with significant incremental hospital and 6-month mortalities. CONCLUSIONS: Frailty is a frequent occurrence and is independently associated with increased ICU and 6-month mortalities. Notably, the CFS predicts outcomes more effectively than the commonly used ICU illness scores.