Setsuro Ogawa

Effects of presurgical local infiltration of bupivacaine in the surgical field on postsurgical wound pain in laparoscopic gynecologic examinations: a possible preemptive analgesic effect.

OBJECTIVE A randomized, double-blind, controlled study was designed to evaluate the effect of presurgical local infiltration of bupivacaine in the surgical field on postsurgical wound pain relief and analgesic requirements in 28 healthy patients scheduled for laparoscopic gynecologic examinations. INTERVENTIONS After induction of general anesthesia by routine methods, the patients were randomly divided into two groups. In the bupivacaine (B) group (n = 15), patients were injected with 5 ml of 0.25% bupivacaine at each incisional area (four sites, total of 20 ml) approximately 15 minutes before skin incision. In the control (C) group (n = 13), the surgical field was injected with an equal volume of physiologic saline solution (four sites, total of 20 ml). OUTCOME MEASURES Postsurgical wound pain at rest was evaluated by a 10-cm visual analog pain scale at 1, 10, 24, and 72 hours and 1 month after surgery. The patients were interviewed via telephone 1 month after hospital discharge for re-evaluation of resting pain. RESULTS The results indicated that the incidence of postsurgical wound pain for up to 10 hours after surgery in group B was significantly lower (p < 0.05) than in group C. Pain intensity ranged from mild to moderate (2-5 cm). In addition, the mean visual analog pain scale pain intensity was significantly less for group B (0.31 +/- 0.85 cm) than for group C (2.62 +/- 2.06 cm) for up to 10 hours after surgery (p < 0.05). The number of patients who requested analgesics and complained of sleep disturbances was significantly higher in group C (p < 0.05). The mean cumulative dose of diclofenac sodium at 24 hours was significantly (p < 0.05) lower in group B (6.67 +/- 17.6 mg) than in group C (30.8 +/- 25.3 mg). Prolonged postsurgical wound pain persisting 1 month after surgery was observed in one patient in group C. CONCLUSIONS It is concluded that presurgical infiltration of 0.25% bupivacaine in the surgical field is a useful method for decreasing postsurgical wound pain for up to 10 hours and analgesic consumption for up to 24 hours after laparoscopic gynecologic examination.

Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.

BACKGROUND: In Japan, routine clinical care does not normally involve the use of a monitoring device to guide the administration of neuromuscular blocking drugs or their antagonists. Although most previous reports demonstrate that sugammadex offers more rapid and reliable antagonism from rocuronium-induced neuromuscular blockade, this advantage has not been confirmed in clinical settings when no neuromuscular monitoring is used. In this multicenter observational study, we sought to determine whether sugammadex reduces the incidence of postoperative residual weakness compared with neostigmine when the administration of rocuronium and its antagonists is not guided by neuromuscular monitoring. METHODS: This study was conducted in two 5-month periods that preceded and followed the introduction of sugammadex into clinical practice in Japan. Five university-affiliated teaching hospitals participated in this study. Neostigmine was used to antagonize rocuronium-induced neuromuscular blockade in the first phase, and sugammadex was used in the second phase. The timing and doses of rocuronium, neostigmine, and sugammadex were determined by the attending anesthesiologists without the use of neuromuscular function monitoring devices. To ascertain the incidence of postoperative residual neuromuscular weakness, the train-of-four ratio (TOFR) was determined acceleromyographically after tracheal extubation. Since our practice also does not usually involve calibration and normalization of accelerographic responses, both TOFR <0.9 and TOFR <1.0 were used as the criteria for defining postoperative residual weakness. RESULTS: In the first phase, 109 patients received neostigmine (average dose 33 µg/kg) and 23 patients were considered (by clinical criteria) to have adequate recovery and did not receive neostigmine (spontaneous recovery group). In the second phase, 117 patients received sugammadex (average dose 2.7 mg/kg) for antagonism of rocuronium-induced blockade. The incidence (95% confidence interval) of TOFR <0.9 under spontaneous recovery, after neostigmine, and after sugammadex, was 13.0% (2.8%–33.6%), 23.9% (16.2%–33.0%), and 4.3% (1.7%–9.4%), respectively. The incidence (95% confidence interval) of TOFR <1.0 in these groups was 69.6% (47.1%–86.6%), 67.0% (57.3%–75.7%), and 46.2% (36.9%–55.6%), respectively. The use of sevoflurane in the neostigmine group and the short interval between the administration of the last doses of rocuronium and sugammadex were associated with a higher incidence of postoperative residual weakness. CONCLUSIONS: This study demonstrated that the risk of TOFR <0.9 after tracheal extubation after sugammadex remains as high as 9.4% in a clinical setting in which neuromuscular monitoring (objective or subjective) was not used. Our finding underscores the importance of neuromuscular monitoring even when sugammadex is used for antagonism of rocuronium-induced neuromuscular block.

Central Hypervolemia with Hemodilution Impairs Dynamic Cerebral Autoregulation

BACKGROUND:Frequent changes in the perioperative central blood volume could affect cerebral autoregulation through alterations in sympathetic nerve activity, cardiac output, blood viscosity, and cerebral vasomotor tone. However, the effect of dynamic cerebral autoregulation has not been studied during acute wide-ranging changes in central blood volume, especially with respect to central hypervolemia with hemodilution. METHODS:We evaluated dynamic cerebral autoregulation during central hypovolemia and central hypervolemia with hemodilution using spectral and transfer function analysis between mean arterial blood pressure (MBP) and cerebral blood flow (CBF) velocity variability in 12 individuals. Rapid changes in central blood volume were achieved using two levels of lower body negative pressure (−15 and −30 mm Hg) and two discrete infusions of normal saline (15 mL/kg and total 30 mL/kg). We then estimated changes in central blood volume as central venous pressure (CVP) and/or cardiac output using impedance cardiography. RESULTS:Steady-state CBF velocity and cardiac output decreased at −30 mm Hg lower body negative pressure (changes of CVP approximately −4 mm Hg) or were increased by each saline infusion (changes of CVP 4–6 mm Hg), without a significant change in MBP. However, transfer function gain (magnitude of transfer) between MBP and CBF velocity variability significantly increased only after saline infusion, suggesting an increased magnitude of transfer from MBP oscillations to CBF fluctuations during central hypervolemia with hemodilution. CONCLUSION:Our results suggest that, although steady-state CBF velocity changes under both central hypervolemia and hypovolemia, only hypervolemic hemodilution impairs dynamic cerebral autoregulation.

Pregabalin Treatment for Peripheral Neuropathic Pain

Two well-studied conditions of peripheral neuropathic pain are postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Several pregabalin trials for peripheral neuropathic pain have been conducted in the West, but limited data are available for Japan. As ethnicity may influence health risks, differences may be evident in safety data from pregabalin trials in Japan and in the West.The objectives of this review were to compare large pooled safety data from randomized controlled trials evaluating pregabalin for the treatment of PHN or DPN in the West with data from two (one PHN, N = 371; one DPN, N = 314) similar trials in Japan. Longer-term safety data from Japanese open-label extension studies were also reviewed in these neuropathic pain populations. Published and unpublished Pfizer-supported pregabalin trials were identified and sourced from internal Pfizer records.A PubMed search to check for inclusiveness was conducted on 2 November 2011 using the following criteria: ‘diabetic peripheral neuropathy’ OR ‘postherpetic neuralgia’ OR ‘neuropathic pain’ AND ‘pregabalin’, with limits set for clinical and randomized controlled trials published in English. Five PHN trials (N= 1250) and nine DPN trials (N = 2554) were identified as suitable for inclusion based on methodological comparability. Descriptive safety data from the original trials were reviewed and the most commonly reported adverse events (AEs; dizziness, somnolence, peripheral oedema and weight gain) were identified to be of primary interest. The majority of AEs were of mild to moderate severity in Japanese and Western populations. The most commonly reported AE data (all-causality) with pregabalin (regardless of dose) in Japan (dizziness: PHN = 31.1%; DPN = 24.6%, and somnolence: PHN = 28.6%; DPN = 25.7%) were compared with pooled data from the Western trials (dizziness: PHN = 24.9%; DPN = 23.0%, and somnolence: PHN=15.1%; DPN=13.4%). Further assessment of these pooled AE (all-causality) data showed that dizziness and somnolence appeared early in the course of pregabalin treatment, but resolved before the end of the treatment in the majority of PHN and DPN patients (maximum duration of trials was 13 weeks).The slightly higher incidence of dizziness and somnolence in the two Japanese trials than that seen in the Western trials may reflect an increased exposure to pregabalin per fixed dose due to the lower mean bodyweight of the Japanese versus Western populations (on a mg/kg basis). However, of the participants who experienced these AEs (all-causality), the proportion who withdrew from the trials in Japan (dizziness: PHN = 23.5%; DPN = 18.2%, and somnolence: PHN = 10.3%; DPN = 10.9%) were comparable with the proportion who withdrew from trials in the West (dizziness: PHN= 16.0%; DPN = 29.3%, and somnolence: PHN = 19.4%; DPN = 34.2%). In Japan, 12.5% (PHN) and 15.1% (DPN) of patients experienced peripheral oedema as an AE (all-causality) compared with 8.8% (PHN) and 10.3% (DPN) in the West. Weight gain as an AE (all-causality) was experienced in 11.7% (PHN) and 13.4% (DPN) of patients in Japan compared with 3.8% (PHN) and 7.0% (DPN) in the West, but stabilized with continued treatment. Despite the lower mean bodyweight in Japanese versus Western patients, the PHN and DPN patients in Japan had stable blood glucose and HbA1c levels throughout the trials.The results of this review indicate safety outcomes in pregabalin trials are comparable between patients in Japan and those in the West. While managing peripheral neuropathic pain with pregabalin treatment, all patients should be observed closely for the incidence of dizziness and somnolence, especially at the beginning of treatment. These patients should also be monitored for evidence of peripheral oedema and weight gain during stable treatment, regardless of the source of neuropathic pain.

Dexmedetomidine Weakens Dynamic Cerebral Autoregulation as Assessed by Transfer Function Analysis and the Thigh Cuff Method

Background:Dexmedetomidine, which is often used in intensive care units in patients with compromised circulation, might induce further severe decreases in cerebral blood flow (CBF) with temporal decreases in arterial pressure induced by various stimuli if dynamic cerebral autoregulation is not improved. Therefore, the authors hypothesized that dexmedetomidine strengthens dynamic cerebral autoregulation. Methods:Fourteen healthy male subjects received placebo, low-dose dexmedetomidine (loading, 3 &mgr;g · kg−1 · h−1 for 10 min; maintenance, 0.2 &mgr;g · kg−1 · h−1 for 60 min), and high-dose dexmedetomidine (loading, 6 &mgr;g · kg−1 · h−1 for 10 min; maintenance, 0.4 &mgr;g · kg−1 · h−1 for 60 min) infusions in a randomized, double-blind, crossover study. After 70 min of drug administration, dynamic cerebral autoregulation was estimated by transfer function analysis between arterial pressure variability and CBF velocity variability, and the thigh cuff method. Results:Compared with placebo, steady state CBF velocity and mean blood pressure significantly decreased during administration of dexmedetomidine. Transfer function gain in the very-low-frequency range increased and phase in the low-frequency range decreased significantly, suggesting alterations in dynamic cerebral autoregulation in lower frequency ranges. Moreover, the dynamic rate of regulation and percentage restoration in CBF velocity significantly decreased when a temporal decrease in arterial pressure was induced by thigh cuff release. Conclusion:Contrary to the authors’ hypothesis, the current results of two experimental analyses suggest together that dexmedetomidine weakens dynamic cerebral autoregulation and delays restoration in CBF velocity during conditions of decreased steady state CBF velocity. Therefore, dexmedetomidine may lead to further sustained reductions in CBF during temporal decreases in arterial pressure.

The Different Effects of Midazolam and Propofol Sedation on Dynamic Cerebral Autoregulation

BACKGROUND: Although midazolam and propofol reduce cerebral blood flow (CBF) similarly, they generate different effects on the autonomic nervous system and endothelium-induced relaxation. Midazolam induces sympathetic dominance, whereas propofol induces parasympathetic dominance. Midazolam has no effect on endothelium-dependent relaxation, whereas propofol suppresses endothelium-dependent relaxation. Moreover, midazolam apparently constricts cerebral arterioles. We therefore hypothesized that midazolam and propofol have different effects on dynamic cerebral autoregulation. METHODS: Ten healthy male subjects received midazolam, propofol, and placebo administrations in a randomized, single-blind, crossover study. The modified Observers Assessment of Alertness/Sedation scale was used to assess sedation depth. After reaching a target depth of sedation (Observers Assessment of Alertness/Sedation scale score 3, responds only after name is called loudly and/or repeatedly) or after 15 minutes of normal saline administration as placebo, dynamic cerebral autoregulation was evaluated by spectral and transfer function analyses between mean arterial blood pressure variability in the radial artery measured by tonometry, and CBF velocity variability in the middle cerebral artery measured by transcranial Doppler ultrasonography. RESULTS: Steady-state CBF velocity decreased significantly with midazolam and propofol administration (significant interaction effects, P = 0.024). However, transfer function gain in the low-frequency range decreased significantly only with midazolam administration (significant interaction effects, P = 0.015), suggesting a reduced magnitude of transfer from mean arterial blood pressure oscillations to CBF fluctuations during midazolam sedation. CONCLUSION: Our results suggest that midazolam and propofol sedation have different effects on dynamic cerebral autoregulation despite causing equivalent decreases in steady-state CBF velocity. Only midazolam sedation is likely to improve dynamic cerebral autoregulation.

The effect of sevoflurane on dynamic cerebral blood flow autoregulation assessed by spectral and transfer function analysis

Sevoflurane reduces autonomic neural control, which plays a significant role in cerebral autoregulation. Therefore, we hypothesized that sevoflurane influences cerebral autoregulation. We investigated the effects of sevoflurane on dynamic cerebral blood flow (CBF) autoregulation by using spectral and transfer function analysis between blood pressure variability and CBF velocity variability. Eleven healthy male subjects received 0.5%, 1.0%, and 1.5% sevoflurane via facemask. Dynamic cerebral autoregulation was evaluated by transfer function gain, phase, and coherence between CBF velocity in the middle cerebral artery measured by transcranial Doppler, and blood pressure in the radial artery. Coherence in the very low-frequency range (0.02–0.07 Hz) increased above 0.5 during administration of 0.5% and 1.0% sevoflurane. Transfer function gain in this frequency range (0.02–0.07 Hz), as an index of dynamic cerebral autoregulation, increased significantly with 0.5% and 1.0% sevoflurane. Transfer function gain and coherence in the low- and high-frequency ranges, however, remained unchanged during administration of sevoflurane. These results suggest that sevoflurane impairs dynamic cerebral autoregulation in the very-low-frequency range even with small concentrations, whereas dynamic cerebral autoregulation in the low- and high-frequency ranges remained unchanged.

Non-invasive assessment of human baroreflex during different body positions.

Two techniques for evaluating human baroreflex sensitivity (BRS), i.e. the sequence technique and the cross-spectral technique, were compared during the following four different body positions; 6 degrees head-down tilt (HDT), supine (Sup), 60 degrees head-up tilt (HUT) and upright (Upr). The sequence technique is based on the slope of linear regression between beat-to-beat RR intervals and systolic blood pressures. The cross-spectral technique is based on the cross-spectral analysis of RR interval and systolic blood pressure variabilities, and the estimates of BRS were computed separately for the low-frequency region (0.04-0.15 Hz) and the high-frequency region (0.15-0.5 Hz). The BRS obtained by the sequence technique had a significant correlation to that obtained by the cross-spectral technique for the low-frequency region in HDT, Sup and HUT, but not in Upr. There was a significant correlation between the BRS obtained by the sequence technique and that obtained by the cross-spectral technique for the high-frequency region in every body position. It became clear that the sequence technique is mutually related to the cross-spectral technique for the high-frequency region, but not necessarily identical to the cross-spectral technique for the low-frequency region. Moreover, a comparison was also made between the baroreceptor activating sequence and the deactivating sequence in the sequence technique during the four different body positions. Although the estimates of BRS of the activating sequence and the deactivating sequence were similar in every body position, the numbers of their sequences were progressively separated in the order of HDT, Sup, HUT and Upr. The numbers of the activating sequence and the deactivating sequence in the sequence technique were found to be separated in a sympathetically dominant condition.

Successful Pain Management of Primary and Independent Spread Sites in a Child with CRPS Type I Using Regional Nerve Blocks

Dear Editor, A 14-year-old girl reported severe pain of the left first toe after a sprain of the left ankle joint when she was 9 years old. She complained of continuous pain in her chest, back, abdomen, and left first toe. The pain at all the sites was of a burning type with intensity of 6 on the numerical rating pain scale. She was unable to walk due to pain. Mechanical allodynia was present. Redness and swelling were recognized over the left first toe. …

Effects of low-dose ketamine on neuropathic pain : An electroencephalogram-electrooculogram/behavioral study

Abstract The aim of the present study was to clarify the neurophysiological changes associated with analgesic and behavioral effects of low‐dose ketamine HCl in patients suffering from chronic neuropathic pain. Ten in‐patients with neuropathic pain participated in this single‐blind, placebo‐controlled study after giving written informed consent. Following intravenous injections of a saline solution (placebo), three bolus injections of 5 mg ketamine HCl were administered at 5 min intervals. Changes in pain perception were assessed using a numerical rating scale for pain. Behavioral changes, including psychotomimetic effects, were assessed using the Brief Psychiatric Rating Scale (BPRS). Electroencephalograms (EEG) and electrooculograms (EOG) were recorded continuously throughout the testing period. One minute EEG and closed‐eye eye movements were quantified. The effects of ketamine were evaluated by comparing the neurophysiological and behavioral parameters obtained from the placebo and ketamine trials. Pain reduction was significantly correlated with ketamine‐induced changes in hallucinatory behavior and excitement as measured by the BPRS. Ketamine injections caused a significant decrease in the EEGα amplitude without an accompanying reduction in EEG frequency. The EEGα amplitude reduction at the right central electrode was significantly related to subjective pain relief. Subanesthetic doses of ketamine significantly decreased rapid eye movements, but did not initiate slow eye movements. In conclusion, the present EEG‐EOG/behavioral results indicate that ketamine‐induced failure of neural integration between cortical–subcortical regions induces psychotic symptoms and alters pain perception on neuropathic pain.