Determination of equi-analgesic doses of inhaled methoxyflurane versus intravenous fentanyl using the cold pressor test in volunteers: a randomised, double-blinded, placebo-controlled crossover study.

BACKGROUND: Inhaled methoxyflurane for acute pain relief has demonstrated an analgesic effect superior to placebo. Data comparing methoxyflurane to an opioid are needed. The aim of this study was to determine the equi-analgesic doses of inhaled methoxyflurane vs i.v. fentanyl. Both drugs have an onset within minutes and an analgesic effect of 20-30 min. METHODS: Twelve subjects were included in a randomised, double-blinded, placebo-controlled crossover study with four treatments: placebo (NaCl 0.9%), fentanyl 25 µg i.v., fentanyl 50 µg i.v., or inhaled methoxyflurane 3 ml. The subjects reported pain intensity using the verbal numeric rating scale (VNRS) from 0 to 10 during the cold pressor test (CPT). The CPT was performed before (CPT 1), 5 min (CPT 2), and 20 min (CPT 3) after drug administration. RESULTS: Inhaled methoxyflurane and fentanyl 25 µg reduced VNRS scores significantly compared with placebo at CPT 2 (-1.14 [estimated difference in VNRS between treatment groups with 95% confidence interval {CI}: -1.50 to -0.78]; -1.15 [95% CI: -1.51 to -0.79]; both P<0.001) and CPT 3 (-0.60 [95% CI: -0.96 to -0.24]; -0.84 [95% CI: -1.20 to -0.47]; both P<0.001). There were no significant differences between the two drugs. Methoxyflurane had significantly higher VNRS scores than fentanyl 50 µg at CPT 2 (0.90 [95% CI: 0.54-1.26]; P<0.001) and CPT 3 (0.57 [95% CI: 0.21-0.94]; P<0.001). CONCLUSIONS: Inhaled methoxyflurane 3 ml was equi-analgesic to fentanyl 25 µg i.v. at CPT 2. Both resulted in significantly less pain than placebo. Fentanyl 50 µg i.v. demonstrated analgesia superior to methoxyflurane. CLINICAL TRIAL REGISTRATION: NCT03894800.

The effects of intermittent negative pressure on the lower extremities' peripheral circulation and wound healing in four patients with lower limb ischemia and hard-to-heal leg ulcers: a case report.

Peripheral circulation is severely compromised in the advanced stages of peripheral arterial disease. Recently, it was shown that the application of -40 mmHg intermittent negative pressure (INP) to the lower leg and foot enhances macro- and microcirculation in healthy volunteers. In this case report, we describe the effects of INP treatment on four patients with lower limb ischemia and hard-to-heal leg and foot ulcers. We hypothesized that INP therapy may have beneficial hemodynamic and clinical effects in the patients. Four patients (age range: 61-79 years) with hard-to-heal leg and foot ulcers (6-24 months) and ankle-brachial pressure indices of ≤0.60 on the affected side were included. They were treated with an 8-week intervention period of -40 mmHg INP (10 sec negative pressure and 7 sec atmospheric pressure) on the lower limbs. A custom-made vacuum chamber was used to apply INP to the affected lower leg and foot for 2 h per day. After 8 weeks of INP therapy, one ulcer healed completely, while the other three ulcers were almost completely healed. These cases suggest that INP may facilitate wound healing. The theoretical foundation is that INP assists wound healing by improving blood flow to the small blood vessels in the affected limb, increasing the flow of oxygen and nutrients to the cells.

Tissue oxygen saturation and finger perfusion index in central hypovolemia: influence of pain.

OBJECTIVES: Tissue oxygen saturation and peripheral perfusion index are proposed as early indirect markers of hypovolemia in trauma patients. Hypovolemia is associated with increased sympathetic nervous activity. However, many other stimuli, such as pain, also increase sympathetic activity. Since pain is often present in trauma patients, its effect on the indirect measures of hypovolemia needs to be clarified. The aim of this study was, therefore, to explore the effects of hypovolemia and pain on tissue oxygen saturation (measurement sites: cerebral, deltoid, forearm, and thenar) and finger photoplethysmographic perfusion index. DESIGN: Experimental study. SETTING: University hospital clinical circulation and research laboratory. SUBJECTS: Twenty healthy volunteers. INTERVENTIONS: Central hypovolemia was induced with lower body negative pressure (-60 mm Hg) and pain by the cold pressor test (ice water exposure). Interventions were performed in a 2×2 fashion with the combination of lower body negative pressure or not (normovolemia), and ice water or not (sham). Each subject was thus exposed to four experimental sequences, each lasting for 8 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements were averaged over 30 seconds. For each person and sequence, the minimal value was analyzed. Tissue oxygenation in all measurement sites and finger perfusion index were reduced during hypovolemia/sham compared with normovolemia/sham. Tissue oxygen saturation (except cerebral) and perfusion index were reduced by pain during normovolemia. There was a larger reduction in tissue oxygenation (all measurement sites) and perfusion index during hypovolemia and pain than during normovolemia and pain. CONCLUSIONS: Pain (cold pressor test) reduces tissue oxygen saturation in all measurement sites (except cerebral) and perfusion index. In the presence of pain, tissue oxygen saturation and perfusion index are further reduced by hypovolemia (lower body negative pressure, -60 mm Hg). Thus, pain must be considered when evaluating tissue oxygen saturation and perfusion index as markers of hypovolemia in trauma patients.

Poor agreement between respiratory variations in pulse oximetry photoplethysmographic waveform amplitude and pulse pressure in intensive care unit patients.

BACKGROUND: To identify fluid responsiveness, a correlation between respiratory variations in pulse pressure (DeltaPP) and respiratory variations in pulse oximetry photoplethysmographic waveform amplitude (DeltaPOP) in mechanically ventilated patients has been demonstrated. To evaluate the agreement between the two methods, knowledge about the repeatability of the methods is imperative. However, no such data exist. Based on knowledge of slow oscillation in skin blood flow, the authors hypothesized that the variability of DeltaPOP would be larger than that of DeltaPP when calculations were performed continuously over a long recording period. METHODS: Respiration, continuous invasive blood pressure, pulse oximetry, and skin microcirculation were recorded in 14 mechanically ventilated intensive care unit patients. No intravenous fluid challenges were given, and no other interventions were performed during the measurements. Seventy consecutive comparisons between DeltaPP and DeltaPOP were calculated for each of the 14 patients. RESULTS: For all patients, DeltaPOP was 13.7 +/- 5.8% and DeltaPP was 5.8 +/- 2.6% (P < 0.001). There was a larger intraindividual (8.94 vs. 1.29; P < 0.001) and interindividual (26.01 vs. 5.57; P < 0.001) variance of DeltaPOP than of DeltaPP. In six patients, there was no significant correlation between DeltaPP and DeltaPOP. A Bland-Altman plot showed poor agreement between the two methods. CONCLUSION: A large variability of DeltaPOP and a poor agreement between DeltaPP and DeltaPOP limits DeltaPOP as a tool for evaluation of fluid responsiveness in intensive care unit patients. This is in contrast to DeltaPP, which shows a small variability.