Measurement of the nociceptive flexion reflex threshold in critically ill patients – a randomized observational pilot study

Background Pain detection and treatment is a major challenge in the care of critically ill patients, rendered more complex by the need to take into consideration the risk of insufficient or excessive analgesia. The nociceptive flexion reflex threshold (NFRT) has become the established basis for measuring the level of analgesia in the perioperative context. However, it remains unclear whether NFRT measurement can be usefully applied to mechanically ventilated, analgosedated critically ill patients who are unable to communicate. Therefore, the aim of the present study was to investigate whether there is an association between the NFRT measurement and the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether the NFRT measurement can also detect potential excessive analgesia. Methods This prospective, observational, randomized single-center pilot study included patients admitted to the surgical Intensive Care Unit of University Hospital Ulm, Germany, all of whom were analgosedated and intubated. Major exclusion criteria were defined as the need for the administration of neuromuscular blocking agents or neurological diseases associated with peripheral nerve conduction restriction. Initial NFRT and BPS measurements were conducted within 12 h after admission. A structured pain assessment was performed at least twice daily until extubation throughout the observation period thereafter (Group A: BPS + NFRT, Group B: BPS). Results 114 patients were included in the study. NFRT is associated negatively with BPS. NFRT was almost twice as high in patients with a Richmond Agitation Sedation Scale (RASS) score of -5 than in patients with a RASS score ≥ -4 (RASS -5 – NFRT: 59.40 vs. RASS -4 – NFRT: 29.00, p < 0.001). Conclusions NFRT measurement is associated negatively with the BPS in critically ill patients. NFRT measurement provides guidance for the evaluation of nociceptive processes in patients with RASS scores ≤ −4, in whom analgesia level is often difficult to assess. However, in order to identify excessive analgesia and derive therapeutic consequences, it is necessary to gradually decrease analgesics and sedatives until a stimulus threshold is reached at which the patient does not feel pain. Trial Registration Retrospectively registered in the German Clinical Trials Register, registration number DRKS00021149, date of registration: March 26, 2020. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021149.

Impact of Propofol Bolus Administration on the Nociceptive Flexion Reflex Threshold and Bispectral Index in Children—A Case Series

We analyzed the impact of propofol administration during continuous sedation and analgesia on the nociceptive flexion reflex threshold (NFRT) and Bispectral Index (BIS) in ventilated children. We examined patients who received propofol before planned endotracheal suctioning. Patients were clinically assessed using the modified Face, Legs, Activity, Cry, Consolability (mFLACC) scale and COMFORT-B (Comfort Behavior) scale. We continuously recorded the NFRT and BIS. We recorded 23 propofol administrations in eight patients with an average age of 8.6 ± 3.5 years. The median (minimum-maximum) scores for the mFLACC scale and COMFORT-B scale were 0 (0–5) and 6 (6–17), respectively, before the bolus. The administration of a weight-adjusted propofol bolus of 1.03 ± 0.31 mg/kg resulted in an increase in NFRT and burst-suppression ratio; BIS and electromyogram values decreased. Changes from baseline (95% CI) after propofol bolus administration were BIS −23.9 (−30.8 to −17.1), EMG -10.5 dB (−13.3 to −7.7), SR 14.8 % (5.6 to 24.0) and NFRT 13.6 mA (5.5 to 21.7). Further studies are needed to determine whether sedated children may benefit from objective pain and sedation monitoring with BIS and NFRT.

Nociceptive disorders in patients with microvascular angina pectoris and patients with silent myocardial ischemia

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): North-western State Medical University named after I.I.Mechnikov The purpose of this study was to study the diagnostic value of the nociceptive flexor reflex (NFR) method in patients with MVA and patients with silent myocardial ischemia. Materials and methods. A total of 158 people were examined, including 131 patients with ischemic heart disease and 31 healthy volunteers (control group). Patients with coronary artery disease were represented by three groups: patients with MVA - 49 people (main group), patients with angina pectoris due to atherosclerotic lesions of the coronary arteries - 40 people (comparison group 1), patients with a diagnosis of painless myocardial ischemia (SMI) - 42 people (comparison group 2). To determine pain indicators, the method of nociceptive flexor reflex (NFR) was used during electrical stimulation of the sural nerve (Nicolet Viking (USA)). Results. The coefficient (k) of pain threshold / reflex threshold (Pb / Pr) in the control group of healthy volunteers was 0.94 ± 0.01, which corresponds to the accepted norms (1-0.9) according to literature data. In the study of NFR in patients with MVA, a decrease in the pain threshold, reflex threshold and ratio (Pb / Pr) was revealed. In the MVS group, PB= 9.5 ± 0.58 mA; Pr = 12.1 ± 0.58 mA; Pb / Pr = 0.78 ± 0.02. The pain threshold in patients with MBS turned out to be statistically significantly lower in comparison with comparison group 1 and comparison group 2 and control group (p &lt;0.01; p &lt;0.001; p &lt;0.001, respectively). The reflex threshold in patients with MVA is statistically significantly lower than in comparison group 1, comparison group 2 (SIM) and control group (p &lt;0.02; p &lt;0.001; p &lt;0.01, respectively). In patients with angina pectoris, PB = 13.8 ± 0.31 mA; Pr = 14.8 ± 0.33 mA; Pb / Pr = 0.94 ± 0.01. In patients with SIM, PB = 24.9 ± 0.99 mA; Pr = 22.9 ± 0.79 mA; Pb / Pr = 1.2 ± 0.02. There was a significant increase in the pain threshold, reflex threshold and the pain threshold / reflex threshold ratio in the group of patients with silent myocardial ischemia compared with similar indicators in the control group, the main group and comparison group 1 (p &lt;0.001; p &lt;0.001; p &lt;0.001 respectively). Conclusions. In patients with MVA compared with healthy individuals in the control group and comparison groups, there is a decrease in NFR indices, which indicates the presence of nociceptive disorders. In patients with SIM, the reflex threshold values are lower in value than the pain threshold. Thus, in patients with SIM the muscle response occurs before the onset of the subjective sensation of pain.

Intravenous lidocaine reduces perioperative opioids without negatively affecting the electrical stapedial reflex threshold in pediatric cochlear implants

Background Total intravenous anesthesia (TIVA) with propofol and remifentanil is frequently used for pediatric cochlear implants (CIs) surgery as it does not suppress the electrical stapedial reflex threshold (ESRT). However, high doses of remifentanil exacerbate postoperative pain and increase opioid consumption. Intravenous lidocaine reduces pain and opioid requirement. This study investigated the effect of intravenous lidocaine on perioperative opioid consumption and ESRT in pediatric CIs. Results The mean (95% CI) remifentanil consumption was significantly lower in lidocaine group than in placebo group [0.57 (0.497–0.643) vs 0.69 (0.63–0.75)] μg/kg/min, P = 0.016. The mean (95% CI) propofol consumption was significantly lower in lidocaine group than in placebo group [155.5 (146–165) vs 171 (161–181) μg/kg/min, P = 0.02. MBP and HR were significantly lower after surgical incision, laryngeal mask airway (LMA) removal, and at PACU admission in the lidocaine group compared with the placebo group. The PACU pain score was significantly lower in the lidocaine group compared to the placebo group. The mean (95% CI) pethidine consumption in PACU was significantly lower in the lidocaine group than in the placebo group 7.0 (6.17–7.83) vs. 8.9 (7.84–9.96) mg, P = 0.012. There were no differences between groups regarding ESRT response. Conclusions Intravenous lidocaine infusion reduced perioperative opioid requirements without altering the ESRT in pediatric CIs. Trial registration Clinical registration number: NCT04194294.

Cost-effectiveness of Stockholm3 test and magnetic resonance imaging in prostate cancer screening: a microsimulation study

ObjectiveAssess the cost-effectiveness of no screening and quadrennial magnetic resonance imaging (MRI)-based screening for prostate cancer using either Stockholm3 or prostate-specific antigen (PSA) test as a reflex test.MethodsTest characteristics were estimated from the STHLM3-MR study (NCT03377881). A cost-utility analysis was conducted from a lifetime societal perspective using a microsimulation model for men aged 55-69 in Sweden for no screening and three quadrennial screening strategies, including: PSA≥3ng/mL; and Stockholm3 with reflex test thresholds of PSA≥1.5 and 2ng/mL. Men with a positive test had an MRI, and those MRI positive had combined targeted and systematic biopsies. Predictions included the number of tests, cancer incidence and mortality, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Uncertainties in key parameters were assessed using sensitivity analyses.ResultsCompared with no screening, the screening strategies were predicted to reduce prostate cancer deaths by 7-9% across a lifetime and were considered to be moderate costs per QALY gained in Sweden. Using Stockholm3 with a reflex threshold of PSA≥2ng/mL resulted in a 60% reduction in MRI compared with screening using PSA. This Stockholm3 strategy was cost-effective with a probability of 70% at a cost-effectiveness threshold of €47,218 (500,000 SEK).ConclusionsAll screening strategies were considered to be moderate costs per QALY gained compared with no screening. Screening with Stockholm3 test at a reflex threshold of PSA≥2ng/mL and MRI was predicted to be cost-effective in Sweden. Use of the Stockholm3 test may reduce screening-related harms and costs while maintaining the health benefits from early detection.