Person:

George, Edward

Background: Pain is difficult to assess due to the subjective nature of self-reporting. The lack of objective measures of pain has hampered the development of new treatments as well as the evaluation of current ones. Functional MRI studies of pain have begun to delineate potential brain response signatures that could be used as objective read-outs of pain. Using Diffuse Optical Tomography (DOT), we have shown in the past a distinct DOT signal over the somatosensory cortex to a noxious heat stimulus that could be distinguished from the signal elicited by innocuous mechanical stimuli. Here we further our findings by studying the response to thermal innocuous and noxious stimuli. Methodology/Principal Findings: Innocuous and noxious thermal stimuli were applied to the skin of the face of the first division (ophthalmic) of the trigeminal nerve in healthy volunteers (N = 6). Stimuli temperatures were adjusted for each subject to evoke warm (equivalent to a 3/10) and painful hot (7/10) sensations in a verbal rating scale (0/10 = no/max pain). A set of 26 stimuli (5 sec each) was applied for each temperature with inter-stimulus intervals varied between 8 and 15 sec using a Peltier thermode. A DOT system was used to capture cortical responses on both sides of the head over the primary somatosensory cortical region (S1). For the innocuous stimuli, group results indicated mainly activation on the contralateral side with a weak ipsilateral response. For the noxious stimuli, bilateral activation was observed with comparable amplitudes on both sides. Furthermore, noxious stimuli produced a temporal biphasic response while innocuous stimuli produced a monophasic response. Conclusions/Significance: These results are in accordance with fMRI and our other DOT studies of innocuous mechanical and noxious heat stimuli. The data indicate the differentiation of DOT cortical responses for pain vs. innocuous stimuli that may be useful in assessing objectively acute pain.

Rationale and Objectives: There is evidence that drug addiction is associated with increased physiological and psychological responses to stress. In this pilot functional magnetic resonance imaging (fMRI) study we assessed whether a prototype behavioral addiction, pathological gambling (PG), is likewise associated with an enhanced response to stress. Methods We induced stress by injecting yohimbine (0.2–0.3 mg/kg, IV), an alpha-2 adrenoceptor antagonist that elicits stress-like physiological and psychological effects in humans and in laboratory animals, to four subjects with PG and to five non-gamblers mentally healthy control subjects. Their fMRI brain responses were assessed along with subjective stress and gambling urges ratings. Results: Voxelwise analyses of data sets from individual subjects, utilizing generalized linear model approach, revealed significant left amygdala activation in response to yohimbine across all PG subjects. This amygdala effect was not observed in the five control individuals. Yohimbine elicited subjective stress ratings in both groups with greater (albeit not statically significantly) average response in the PG subjects. On the other hand, yohimbine did not induce urges to gamble. Conclusions: The present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG.

Background: Monitoring the adequacy of spontaneous breathing is a major patient safety concern in the post-operative setting. Monitoring is particularly important for obese patients, who are at a higher risk for post-surgical respiratory complications and often have increased metabolic demand due to excess weight. Here we used a novel, noninvasive Respiratory Volume Monitor (RVM) to monitor ventilation in both obese and non-obese orthopedic patients throughout their perioperative course, in order to develop better monitoring strategies. Methods: We collected respiratory data from 62 orthopedic patients undergoing elective joint replacement surgery under general anesthesia using a bio-impedance based RVM with an electrode PadSet placed on the thorax. Patients were stratified into obese (BMI ≥ 30) and non-obese cohorts and minute ventilation (MV) at various perioperative time points was compared against each patient’s predicted minute ventilation (MVPRED) based on ideal body weight (IBW) and body surface area (BSA). The distributions of MV measurements were also compared across obese and non-obese cohorts. Results: Obese patients had higher MV than the non-obese patients before, during, and after surgery. Measured MV of obese patients was significantly higher than their MVPRED from IBW formulas, with BSA-based MVPRED being a closer estimate. Obese patients also had greater variability in MV post-operatively when treated with standard opioid dosing. Conclusions: Our study demonstrated that obese patients have greater variability in ventilation post-operatively when treated with standard opioid doses, and despite overall higher ventilation, many of them are still at risk for hypoventilation. BSA-based MVPRED formulas may be more appropriate than IBW-based ones when estimating the respiratory demand of obese patients. The RVM allows for the continuous and non-invasive assessment of respiratory function in both obese and non-obese patients.

Obstructive sleep apnea (OSA) is a potential independent risk factor for postoperative complications, adverse surgical outcomes, and longer hospital stays. Obese patients with OSA have increased post-operative complications. An estimated 25-30% of pre-operative patients are at a high risk for OSA. A novel, non-invasive respiratory volume monitor (RVM) has been developed to provide a real time respiratory curve demonstrating lung volumes as well as a continuous, display of minute ventilation, tidal volume and respiratory rate. Clinical application of this device in the post-anesthesia care unit (PACU) can “unmask” post-operative apneic events resulting from partial or complete airway collapse due to the residual effects of narcotic administration and volatile and/or intravenous anesthetics. Clinical examples from two patients, one with known OSA and one without a previous diagnosis of OSA, monitored in the PACU with RVM are presented here. Post-operatively both patients had an increase in apneic episodes with significant decreases in their MV during apneic episodes after opioid administration as compared to pre-op baseline. In addition, oxygen saturation, for both patients, which is an essential component of current respiratory monitoring remained normal in the cases presented, despite the significant decreases in MV. Continuous RVM monitoring demonstrates both changes in respiratory patterns and overall adequacy of ventilation, and allows practitioners to quantify the increase in the number and duration apneic episodes as a response to narcotic administration. These case studies demonstrate that a non-invasive respiratory volume monitoring system can detect and quantify respiratory disturbances that currently go undetected.

Introduction: Obstructive sleep apnea and opioid-induced respiratory depression can unpredictably threaten respiratory competence in the post-anesthesia care unit. Current respiratory monitoring relies heavily on respiratory rate and oxygen saturation, as well as subjective clinical assessment. These assessments have distinct limitations, and none provide a real-time, objective, quantitative direct measurement of respiratory status. A novel, non-invasive respiratory volume monitor uses bioimpedance to provide accurate, quantitative measurements of minute ventilation, tidal volume and respiratory rate continuously in real time, providing a direct measurement of ventilation. Case presentation: The case describes an orthopedic surgery patient (54-year-old Caucasian man, body mass index 33.7kg/m2) with diagnosed obstructive sleep apnea in whom the respiratory volume monitor data depicted persistent apneic behavior undetected by other monitoring. The monitor was able to detect a sudden reduction in minute ventilation after initial opioid administration in the post-anesthesia care unit. The patient had sustained low minute ventilation until discharge. Neither respiratory rate data from the hospital monitor nor oxygen saturation readings reflected the respiratory decompensation, remaining within normal limits even during sustained low minute ventilation. Conclusions: The events of this case illustrate the limitations of current respiratory rate monitoring and pulse oximetry in the evaluation of post-surgical respiratory status. Our patient displayed stable respiratory rate and no evidence of desaturation, despite sustained low minute ventilation, and he received opioids in the post-anesthesia care unit despite already compromised ventilation. Because the available monitoring did not indicate the patient’s true respiratory status, he was treated with additional opioids, markedly increasing his risk for further respiratory decline.