Sam R. Sharar

Effectiveness of virtual reality-based pain control with multiple treatments.

ObjectiveThe current study explored whether immersive virtual reality continues to reduce pain (via distraction) with repeated use. SettingThe study was conducted in a burn care unit at a regional trauma center. PatientsSeven patients aged 9–32 years (mean age of 21.9 years; average of 23.7% total body surface area burned [range, 3–60%]) performed range-of-motion exercises of their injured extremity under an occupational therapists direction on at least 3 separate days each. InterventionFor each physical therapy session, each patient spent equal amounts of time in virtual reality and in the control condition (no distraction). The mean duration of physical therapy in virtual reality was 3.5, 4.9, and 6.4 minutes for the first, second, and third session, respectively. Condition order was randomized and counterbalanced. Outcome MeasuresFor each of the three physical therapy sessions, five visual analog pain scores for each treatment condition served as the dependent variables. ResultsPain ratings were statistically lower when patients were in virtual reality, and the magnitude of pain reduction did not diminish with repeated use of virtual reality. The results of this study may be examined in more detail at www.vrpain.com. ConclusionsAlthough the small sample size limits generalizability, results provide converging preliminary evidence that virtual reality can function as a strong nonpharmacological pain reduction technique for burn patients during physical therapy. Results suggest that virtual reality does not diminish in analgesic effectiveness with three (and possibly more) uses. Virtual reality may also have analgesic potential for other painful procedures or pain populations. Practical implications are discussed.

Virtual reality pain control during burn wound debridement in the hydrotank.

ObjectiveMost burn-injured patients rate their pain during burn wound debridement as severe to excruciating. We explored the adjunctive use of water-friendly, immersive virtual reality (VR) to distract patients from their pain during burn wound debridement in the hydrotherapy tank (hydrotank). SettingThis study was conducted on inpatients at a major regional burn center. PatientsEleven hospitalized inpatients ages 9 to 40 years (mean age, 27 y) had their burn wounds debrided and dressed while partially submerged in the hydrotank. InterventionAlthough a nurse debrided the burn wound, each patient spent 3 minutes of wound care with no distraction and 3 minutes of wound care in VR during a single wound care session (within-subject condition order randomized). Outcome MeasuresThree 0 to 10 graphic rating scale pain scores (worst pain, time spent thinking about pain, and pain unpleasantness) for each of the 2 treatment conditions served as the primary dependent variables. ResultsPatients reported significantly less pain when distracted with VR [eg, “worst pain” ratings during wound care dropped from “severe” (7.6) to “moderate” (5.1)]. The 6 patients who reported the strongest illusion of “going inside” the virtual world reported the greatest analgesic effect of VR on worst pain ratings, dropping from severe pain (7.2) in the no VR condition to mild pain (3.7) during VR. ConclusionsResults provide the first available evidence from a controlled study that immersive VR can be an effective nonpharmacologic pain reduction technique for burn patients experiencing severe to excruciating pain during wound care. The potential applications of VR analgesia to other painful procedures (eg, movement or exercise therapy) and other pain populations are discussed.

Virtual Reality as an Adjunctive Non-pharmacologic Analgesic for Acute Burn Pain During Medical Procedures

IntroductionExcessive pain during medical procedures is a widespread problem but is especially problematic during daily wound care of patients with severe burn injuries.MethodsBurn patients report 35–50% reductions in procedural pain while in a distracting immersive virtual reality, and fMRI brain scans show associated reductions in pain-related brain activity during VR. VR distraction appears to be most effective for patients with the highest pain intensity levels. VR is thought to reduce pain by directing patients’ attention into the virtual world, leaving less attention available to process incoming neural signals from pain receptors.ConclusionsWe review evidence from clinical and laboratory research studies exploring Virtual Reality analgesia, concentrating primarily on the work ongoing within our group. We briefly describe how VR pain distraction systems have been tailored to the unique needs of burn patients to date, and speculate about how VR systems could be tailored to the needs of other patient populations in the future.

Manipulating presence influences the magnitude of virtual reality analgesia.

&NA; Excessive pain during medical procedures performed in unanesthetized patients is frequently reported, but can be reduced with virtual reality (VR) distraction. Increasing the persons illusion of going into the virtual world may increase how effectively VR distracts pain. Healthy volunteers aged 18–20 years participated in a double‐blind between‐groups design. Each subject received a brief baseline thermal pain stimulus, and the same stimulus again minutes later with either a Low Tech or a High Tech VR distraction. Each subject provided subjective 0–10 ratings of cognitive, sensory and affective components of pain, and rated their illusion of going inside the virtual world. Subjects in the High Tech VR group reported a stronger illusion of going into the virtual world (VR presence) than subjects in the Low Tech VR group, (4.2 vs. 2.5, respectively, P=0.009) and more pain reduction (reduction of worst pain is 3.1 for High Tech VR vs. 0.7 for Low Tech VR, P<0.001). Across groups, the amount of pain reduction was positively and significantly correlated with VR presence levels reported by subjects (r=0.48 for ‘worst pain’, P<0.005).

The illusion of presence in immersive virtual reality during an fMRI brain scan.

The essence of immersive virtual reality (VR) is the illusion it gives users that they are inside the computer-generated virtual environment. This unusually strong illusion is theorized to contribute to the successful pain reduction observed in burn patients who go into VR during woundcare (www.vrpain.com) and to successful VR exposure therapy for phobias and post-traumatic stress disorder (PTSD). The present study demonstrated for the first time that subjects could experience a strong illusion of presence during an fMRI despite the constraints of the fMRI magnet bore (i.e., immobilized head and loud ambient noise).

Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task: an FMRI study.

We have used functional MRI to determine the effects of ketamine on brain systems activated in association with a working memory task. Healthy volunteers received intravenous infusions of placebo, ketamine at 50 ng/ml plasma concentration, and ketamine at 100 ng/ml. They were scanned while carrying out a verbal working memory task in which we varied the executive requirements (manipulation vs maintenance processes) and the mnemonic load (three vs five presented letters). We previously showed that ketamine produces a specific behavioral impairment in the manipulation task. In the current study, we modified tasks in order to match performance across drug and placebo conditions, and used an event-related fMRI design, allowing us to remove unsuccessful trials from the analysis. Our results suggest a task-specific effect of ketamine on working memory in a brain system comprising frontal cortex, parietal cortex, and putamen. When subjects are required to manipulate presented letters into alphabetical order, as opposed to maintaining them in the order in which they were presented, ketamine is associated with significantly greater activity in this system, even under these performance-matched conditions. No significant effect of ketamine was seen in association with increasing load. This suggests that our findings are not explicable in terms of a nonspecific effect of ketamine when task difficulty is increased. Rather, our findings provide evidence that the predominant effects of low, subdissociative doses of ketamine are upon the control processes engaged by the manipulation task. Furthermore, we have shown that ketamines effects may be elucidated by fMRI even when overt behavioral measures show no evidence of impairment.

The Analgesic Effects of Opioids and Immersive Virtual Reality Distraction: Evidence from Subjective and Functional Brain Imaging Assessments

BACKGROUND:Immersive virtual reality (VR) is a novel form of distraction analgesia, yet its effects on pain-related brain activity when used adjunctively with opioid analgesics are unknown. We used subjective pain ratings and functional magnetic resonance imaging to measure pain and pain-related brain activity in subjects receiving opioid and/or VR distraction. METHODS:Healthy subjects (n = 9) received thermal pain stimulation and were exposed to four intervention conditions in a within-subjects design: (a) control (no analgesia), (b) opioid administration [hydromorphone (4 ng/mL target plasma level)], (c) immersive VR distraction, and (d) combined opioid + VR. Outcomes included subjective pain reports (0–10 labeled graphic rating scales) and blood oxygen level-dependent assessments of brain activity in five specific, pain-related regions of interest. RESULTS:Opioid alone significantly reduced subjective pain unpleasantness ratings (P < 0.05) and significantly reduced pain-related brain activity in the insula (P < 0.05) and thalmus (P < 0.05). VR alone significantly reduced both worst pain (P < 0.01) and pain unpleasantness (P < 0.01) and significantly reduced pain-related brain activity in the insula (P < 0.05), thalmus (P < 0.05), and SS2 (P < 0.05). Combined opioid + VR reduced pain reports more effectively than did opioid alone on all subjective pain measures (P < 0.01). Patterns of pain-related blood oxygen level-dependent activity were consistent with subjective analgesic reports. CONCLUSIONS:These subjective pain reports and objective functional magnetic resonance imaging results demonstrate converging evidence for the analgesic efficacy of opioid administration alone and VR distraction alone. Furthermore, patterns of pain-related brain activity support the significant subjective analgesic effects of VR distraction when used as an adjunct to opioid analgesia. These results provide preliminary data to support the clinical use of multimodal (e.g., combined pharmacologic and nonpharmacologic) analgesic techniques.

Isoflurane compared with nitrous oxide anaesthesia for intraoperative monitoring of somatosensory-evoked potentials

Intraoperative monitoring of somatosensoryevoked potentials is a routine procedure. To determine the depressant effect of nitrous oxide relative to isoflurane, the authors recorded the scalp, cervical and brachial plexusevoked responses to stimulation of the median nerve under different anaesthetic conditions. Eight subjects, age 35 ± 6 (SD) yr, weight 68 ± 12 kg, were studied. Following recording of awake control responses, anaesthesia was induced with thiopentone 5 mg· kg− 1 and fentanyl 3 μg· kg− 1 and was followed by succinylcholine 1 mg· kg− 1. During normocapnia and normothermia, and with a maintenance infusion of fentanyl 3 μg · kg− 1· hr− 1, evoked potential recording was repeated under three different anaesthetic conditions; 0.6 MAC nitrous oxide, 0.6 MAC nitrous oxide ± 0.6 MAC isoflurane, and 0.6 MAC isoflurane. Among the anaesthetic conditions, the combination of nitrous oxide-isoflurane had the most depressant effect on the cortical amplitude (67 ± 4% reduction, P < 0.05). Nitrous oxide decreased the cortical amplitude more than an equipotent dose of isoflurane (60 ± 4% vs 48 ± 7%, P < 0.05). The latency was unchanged by nitrous oxide, but increased slightly by isoflurane and isofluranenitrous oxide anaesthesia (1.0 and 0.9 msec respectively, P < 0.05). We conclude that somatosensory-evoked potential monitoring is feasible both during nitrous oxide anaesthesia and isoflurane anaesthesia, but the cortical amplitude is better preserved during 0.6 MAC of isoflurane alone relative to 0.6 MAC of nitrous oxide alone. The depressant effect is maximal during nitrous oxideisoflurane anaesthesia but less than the predicted additive effect.RésuméLe monitorage des potentiels évoqués somato-sensoriels est une technique utilisée couramment. Pour comparer les effets dépresseurs du protoxyde d’azote à ceux de l’isoflurane, les auteurs ont enregistré sur le scalp et les plexus cervical et brachial, les réponses évoquées à la stimulation du nerf médian sous différentes méthodes d’anesthésie. Il ont étudié huit sujets, âgés de 35 ± 6 (SD) ans, pesant 68 ± 12 kg. Après l’enregistrement des réponses vigiles (contrôle), l’anesthésie a été induite avec du thiopentone 5 mg· kg− 1 et du fentanyl 3 μg· kg− 1 suivi de succinylcholine 1 mg· kg− 1. Sous normocapnie et normothermie avec une perfusion d’entretien de fentanyl 3 μg· kg− 1· hr− 1, ils ont répété l’enregistrement des potentiels évoqués pendant trois méthodes d’anesthésie: protoxyde d’azote 0,6 MAC, protoxyde d’azote 0,6 MAC + isoflurane 0,6 MAC, et isoflurane 0,6 MAC. Parmi ces méthodes, le protoxyde d’azote-isoflurane a l’effet dépresseur le plus marqué sur l’amplitude corticale (baisse de 67 ± 4%, P < 0,05). Le protoxyde l’azote diminue l’amplitude corticale d’une façon plus importante qu’une concentration équipolente d’isoflurane (60 ± 4% vs 48 ± 7%, P < 0,05). Sous protoxyde d’azote, la période de latence demeure inchangée, mais augmente légèrement sous isoflurane et sous isoflurane-protoxyde d’azote (1,0 et 0,9 MAC respectivement, P < 0,05). Les auteurs concluent que le monitorage des potentiels somato-sensoriels évoqués est réalisable pendant l’anesthésie au protoxyde d’azote et à l’isoflurane, mais que l’amplitude est mieux préservée pendant 0,6 MAC d’isoflurane seul comparativement à 0,6 MAC de protoxyde d’azote. L’effet dépresseur est maximal pendant l’anesthésie au protoxyde-isoflurane mais il est moindre que la somme arithmétique des effets de chacune des substances.

Lorazepam as an adjunct to opioid analgesics in the treatment of burn pain

Abstract Benzodiazepines are commonly used to supplement opioid analgesics in treating procedural pain during the treatment of major burn injuries. To date, no study has investigated whether benzodiazepines actually have an analgesic or anxiolytic effect in such circumstances. Seventy‐nine patients admitted to a major regional burn center were randomly assigned to groups that received 1 mg of lorazepam or a placebo in addition to their standard opioid analgesics. A strong analgesic effect of lorazepam was not observed when treatment groups were compared independent of their baseline pain ratings. However when patients who had high baseline pain were compared, lorazepam resulted in a significant reduction in pain ratings (adjusted post‐treatment VAS mean score=54.28; adjusted control VAS mean score=69.06). Trait anxiety did not predict those patients who had an analgesic effect with lorazepam, but state anxiety did prove to be a covariate with visual analogue score decreases in pain reports.

CD18 adhesion blockade decreases bacterial clearance and neutrophil recruitment after intrapulmonary E. coli, but not after S. aureus.

Leukocyte emigration in the lung occurs by both CD18‐dependent and ‐independent mechanisms that are stimulus specific. We examined the effect of CD18 blockade (mAb 60.3) on neutrophil (PMN) emigration into, and bacterial clearance from, the lung. After intravenous treatment with either mAb 60.3 or saline, rabbits were given an intralobar inoculation with 109 colony‐forming units of either Staphylococcus aureus or Escherichia coli. Four hours after inoculation, lungs were lavaged to assess PMN emigration. CD18 blockade reduced PMN emigration to E. coli by 76% but only 45% to S. aureus. Experiments to determine bacterial recovery from the lungs at 4, 8, and 24 h after inoculation showed that CD18 blockade impaired the early (4 h) clearance of E. coli but not S. aureus. These findings suggest that PMN emigration to intrapulmonary S. aureus is largely CD18‐independent. In contrast, intrapulmonary E. coli elicits CD18‐mediated PMN emigration. CD18 blockade results in impaired clearance of E. coli but not S. aureus from the lung. J. Leukoc. Biol. 61: 167–172; 1997.