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.

Effects of Transcutaneous Spinal Direct Current Stimulation (tsDCS) in Patients With Chronic Pain: A Clinical and Neurophysiological Study

Background and Aims: Chronic pain is a complex clinical condition, often devastating for patients and unmanageable with pharmacological treatments. Converging evidence suggests that transcutaneous spinal Direct Current Stimulation (tsDCS) might represent a complementary therapy in managing chronic pain. In this randomized, double-blind and sham-controlled crossover study, we assessed tsDCS effects in chronic pain patients.Methods: Sixteen patients (aged 65.06 ± 16.16 years, eight women) with chronic pain of different etiology underwent sham and anodal tsDCS (anode over the tenth thoracic vertebra, cathode over the somatosensory cortical area: 2.5 mA, 20 min, 5 days for 1 week). As outcomes, we considered the Visual Analog Scale (VAS), the Neuropathic Pain Symptom Inventory (NPSI), and the components of the lower limb flexion reflex (LLFR), i.e., RIII threshold, RII latency and area, RIII latency and area, and flexion reflex (FR) total area. Assessments were conducted before (T0), immediately at the end of the treatment (T1), after 1 week (T2) and 1 month (T3).Results: Compared to sham, anodal tsDCS reduced RIII area at T2 (p = 0.0043) and T3 (p = 0.0012); similarly, FR total area was reduced at T3 (p = 0.03). Clinically, anodal tsDCS dampened VAS at T3 (p = 0.015), and NPSI scores at T1 (p = 0.0012), and T3 (p = 0.0015), whereas sham condition left them unchanged. Changes in VAS and NPSI scores linearly correlated with the reduction in LLFR areas (p = 0.0004).Conclusions: Our findings suggest that tsDCS could modulate nociceptive processing and pain perception in chronic pain syndromes.

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.

Measurement of the nociceptive flexion reflex threshold in critically ill patients - a monocentric prospective observational study

Background Pain detection and treatment is a major challenge in the care of critically ill patients. However, in addition to the risk of analgesic undersupply, there is also the risk of overanalgesia. In the perioperative context, the measurement of the nociceptive flexion reflex threshold has become established for measuring the level of analgesia. To date, however, it is unclear whether measurement of NFRT can be usefully applied to noncommunicating, ventilated, and analgosedated ICU patients. Therefore, the aim of the present study was to investigate whether NFRT measurement correlates with the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether it can also detect possible overanalgesia.Methods In this prospective, observational, single-center study, 114 patients were included. All patients were admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany. First measurements of the NFRT and the Behavioral Pain Scale (BPS) were conducted within 12 hours after admission. In the further observation period, a structured pain assessment was performed at least twice daily until extubation (Group A: BPS + NFRT, Group B: BPS). Univariate analysis was performed to evaluate possible associations between NFRT measurement and baseline characteristics. Furthermore, mixed linear regression modeling was used to evaluate possible effects of administered analgesics or sedatives on NFRT. Results NFRT correlates negatively with the Behavioral Pain Scale. NFRT was almost twice as high in patients with a RASS of -5 compared with patients with a RASS ≥ -4 (RASS -5 - NFRT: 59.40 vs. RASS -4 - NFRT: 29.00, p < 0.001). By means of NFRT measurement, potential overanalgesia could not be detected.Conclusion The NFRT measurement reliably correlates negatively with the Behavioral Pain Scale in critically ill patients. In patients with RASS scores ≤ -4, in whom analgesia level is often difficult to assess, NFRT measurement provides guidance in the assessment of nociceptive processes. However, in order to detect possible overanalgesia and to derive therapeutic consequences, a defined stimulus threshold must be determined for the critically ill patient, above which the absence of pain can be safely assumed.Trial Registration Retrospectively registered at 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