COX-2 inhibition: what we learned--a controversial update on safety data.

IMPORTANCE: Cyclooxygenase type 2 (COX-2)-selective nonsteroidal anti-inflammatory drugs (NSAIDs) (c2sNSAIDs) have been scrutinized relative to the less costly nonselective NSAIDs (nsNSAIDs). The conclusions reached were not always consistent with the data, and best treatment choices for patients were not always recommended. OBJECTIVE: The data that were used to criticize the c2sNSAIDs are reexamined in a controversial light, demonstrating that the presence of reverse bias was often, but not always, present. EVIDENCE REVIEW: A review of both Pubmed and news media articles relating to nsNSAIDs and c2sNSAIDs was conducted. References were selected on the basis of relevance to the controversies. FINDINGS: The initial claims for the c2sNSAIDs of reduced gastrointestinal (GI) injury and preservation of platelet function were soon dwarfed by concerns regarding increased cardiovascular (CV) risk with publication of the Vioxx Gastrointestinal Outcomes Research trial for rofecoxib. Initial prothrombotic theories had a poor basis for explaining these concerns and have since largely been replaced with more credible explanations, including blood pressure elevations known to occur with all NSAIDs. Between data suggesting increased CV risk and under political pressure and public outcry, rofecoxib was withdrawn from the market in 2004. Soon, all c2sNSAIDs were under scrutiny. The Food and Drug Administration has since grouped all NSAIDs, whether c2sNSAID or nsNSAID, into one class with similar warnings regarding skin, CV, renal, and GI side effects. CONCLUSIONS AND RELEVANCE: The entire "COX-2 debacle" is reminiscent of past events with NSAIDs. Amid this public, media, and political hysteria, it is not clear if we will see any more NSAIDs (selective or otherwise) approved in the near future.

Prescription patterns of pain medicine physicians.

OBJECTIVES: Our study surveyed physician members of 3 American pain societies to determine prescription patterns and whether these practices reflect current expert opinion. METHODS: We sent 3 mailings to 2938 physicians from January 2010 to January 2011. The questionnaire contained 49 questions on topics related to opioids, antidepressants, anticonvulsants, and preferences for the different pain syndromes. RESULTS: A total of 474 physicians responded, representing a 16% return. Seventy-two percent ask patients to sign an opioid agreement, 59% order random urine drug testing, 13% wait until the dose of methadone is between 100 and 150 mg before converting the drug to another opioid, and 85% do not think there is a maximum dose of opioids with respect to driving. Most responders prescribe codeine to Caucasians and Asians. While 42% stated that the maximum daily dose of acetaminophen is 3000 mg, 75% would decrease the dose in patients who are moderate or heavy drinkers. Fifty-four percent do not order an ECG at all when prescribing tricyclic antidepressants. CONCLUSIONS: The responses pertaining to opioid agreements, urine drug testing, acetaminophen, and treatment for neuropathic pain are reassuring in that they prevent misuse and abuse of opioids, prevent acetaminophen-induced hepatotoxicity, and reflect evidence-based treatments. However, we identified gaps in knowledge, including the prescription of codeine in certain populations and the use of electrocardiogram in patients on antidepressants. Further education of physicians who treat chronic pain pharmacologically is warranted.

Integrating Radiomics With Clinicoradiological Scoring Can Predict High-Risk Patients Who Need Surgery in Crohn's Disease: A Pilot Study.

BACKGROUND: Early identification of Crohn's disease (CD) patients at risk for complications could enable targeted surgical referral, but routine magnetic resonance enterography (MRE) has not been definitively correlated with need for surgery. Our objective was to identify computer-extracted image (radiomic) features from MRE associated with risk of surgery in CD and combine them with clinical and radiological assessments to predict time to intervention. METHODS: This was a retrospective single-center pilot study of CD patients who had an MRE within 3 months prior to initiating medical therapy. Radiomic features were extracted from annotated terminal ileum regions on MRE and combined with clinical variables and radiological assessment (via Simplified Magnetic Resonance Index of Activity scoring for wall thickening, edema, fat stranding, ulcers) in a random forest classifier. The primary endpoint was high- and low-risk groups based on need for surgery within 1 year of MRE. The secondary endpoint was time to surgery after treatment. RESULTS: Eight radiomic features capturing localized texture heterogeneity within the terminal ileum were significantly associated with risk of surgery within 1 year of treatment (P < .05); yielding a discovery cohort area under the receiver-operating characteristic curve of 0.67 (n = 50) and validation cohort area under the receiver-operating characteristic curve of 0.74 (n = 23). Kaplan-Meier analysis of radiomic features together with clinical variables and Simplified Magnetic Resonance Index of Activity scores yielded the best hazard ratio of 4.13 (P = (7.6 × 10-6) and concordance index of 0.71 in predicting time to surgery after MRE. CONCLUSIONS: Radiomic features on MRE may be associated with risk of surgery in CD, and in combination with clinicoradiological scoring can yield an accurate prognostic model for time to surgery.

"Zombielike" Aggression in Perampanel Overdose.

Perampanel is an antiepileptic drug that blocks amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. To date, little is known about the management of perampanel intoxication. We report a case of "zombielike" behavior secondary to intentional perampanel overdose. An 18-year-old male with idiopathic generalized epilepsy and focal features presented with aggressive and "zombielike" behavior after suicide attempt via intentional perampanel overdose, amounting to approximately 128 mg. Clinical symptoms gradually improved with continuous dexmedetomidine infusion and intravenous lorazepam boluses five days after being admitted to the intensive care unit. While perampanel intoxication has been reported to be associated with central nervous system-related adverse effects, awareness of this association is necessary to prompt more appropriate management tailored to perampanel toxicity.

Incidence of intradiscal injection during lumbar fluoroscopically guided transforaminal and interlaminar epidural steroid injections.

Intradiscal injections during transforaminal epidural steroid injections and interlaminar lumbar epidural steroid injections have been reported rarely. In that regard, this retrospective observational report is the first attempt to quantify the overall rate of this complication. A retrospective analysis of 3 years of accrued data (2004-2007) showed that 2412 transforaminal epidural steroid injections were performed at the 2 training institutions (Loyola University Medical Center and Northwestern University/Feinberg School of Medicine). There were 6 intradiscal (annular) injections of contrast, for a rate of 1:402. Over the same interval, 4723 lumbar epidural steroid injections were performed, with 1 intradiscal injection, for a rate of 1:4723.

Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial.

BACKGROUND & AIMS: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC). METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>/=2-point reduction) at week 12. Clinical remission (Mayo score

The spontaneous breathing pattern and work of breathing of patients with acute respiratory distress syndrome and acute lung injury.

BACKGROUND: The spontaneous breathing pattern and its relationship to compliance, resistance, and work of breathing (WOB) has not been examined in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). Clinically, the ratio of respiratory frequency to tidal volume (f/VT) during spontaneous breathing may reflect adaptation to altered compliance, resistance, and increased WOB. We examined the relationship between f/VT, WOB, and respiratory system mechanics in patients with ARDS/ALI. METHODS: Data from spontaneous breathing trials were collected from 33 patients (20 with ARDS, 13 with ALI) at various points in their disease course. WOB and respiratory system mechanics were measured with a pulmonary mechanics monitor that incorporates Campbell diagram software. Differences between the patients with ARDS and ALI were assessed with 2-sided unpaired t tests. Multivariate linear regression models were constructed to assess the relationship between f/VT and other pulmonary-related variables. RESULTS: Patients with ARDS had significantly lower compliance than those with ALI (24 +/- 6 mL/cm H2O vs 40 +/- 13 mL/cm H2O, respectively, p < 0.001), but this did not translate into significant differences in either WOB (1.70 +/- 0.59 J/L vs 1.43 +/- 0.90 J/L, respectively, p = 0.30) or f/VT (137 +/- 82 vs 107 +/- 49, respectively, p = 0.23). Multivariate linear regression modeling revealed that peak negative esophageal pressure, central respiratory drive, duration of ARDS/ALI, minute ventilation deficit between mechanical ventilation and spontaneous breathing, and female gender were the strongest predictors of f/VT. CONCLUSION: The characteristic rapid shallow breathing pattern in patients with ARDS/ALI occurs in the context of markedly diminished compliance, elevated respiratory drive, and increased WOB. That f/VT had a strong, inverse relationship to peak negative esophageal pressure also may reflect the influence of muscle weakness.

Work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome: a comparison between volume and pressure-regulated breathing modes.

BACKGROUND: Pressure-control ventilation (PCV) and pressure-regulated volume-control (PRVC) ventilation are used during lung-protective ventilation because the high, variable, peak inspiratory flow rate (V (I)) may reduce patient work of breathing (WOB) more than the fixed V (I) of volume-control ventilation (VCV). Patient-triggered breaths during PCV and PRVC may result in excessive tidal volume (V(T)) delivery unless the inspiratory pressure is reduced, which in turn may decrease the peak V (I). We tested whether PCV and PRVC reduce WOB better than VCV with a high, fixed peak V (I) (75 L/min) while also maintaining a low V(T) target. METHODS: Fourteen nonconsecutive patients with acute lung injury or acute respiratory distress syndrome were studied prospectively, using a random presentation of ventilator modes in a crossover, repeated-measures design. A target V(T) of 6.4 + 0.5 mL/kg was set during VCV and PRVC. During PCV the inspiratory pressure was set to achieve the same V(T). WOB and other variables were measured with a pulmonary mechanics monitor (Bicore CP-100). RESULTS: There was a nonsignificant trend toward higher WOB (in J/L) during PCV (1.27 + 0.58 J/L) and PRVC (1.35 + 0.60 J/L), compared to VCV (1.09 + 0.59 J/L). While mean V(T) was not statistically different between modes, in 40% of patients, V(T) markedly exceeded the lung-protective ventilation target during PRVC and PCV. CONCLUSIONS: During lung-protective ventilation, PCV and PRVC offer no advantage in reducing WOB, compared to VCV with a high flow rate, and in some patients did not allow control of V(T) to be as precise.

The effects of tidal volume demand on work of breathing during simulated lung-protective ventilation.

BACKGROUND: Lung-protective ventilation (LPV) can result in a ventilator tidal volume (V(T)) below patient V(T) demand, which may elevate work of breathing (WOB). Increasing the ventilator inspiratory flow may not sufficiently reduce WOB, because the patient's flow-time requirements may exceed the ventilator's flow-time delivery pattern. We investigated (1) the effects of V(T) demand on WOB during LPV and (2) which ventilator pattern best reduced WOB while achieving LPV goals. METHODS: A standard WOB lung model simulated assisted breathing. Using 3 ventilators (Hamilton Veolar, Hamilton Galileo, and Dräger Evita 2 dura), we tested volume-control ventilation with a constant flow pattern (VCV-CF), volume-control ventilation with a decelerating flow (VCV-DF), and pressure-control ventilation (PCV). Simulated V(T) demand was increased from 50-125% of the ventilator-delivered V(T) (400 mL) as ventilator inspiratory time (T(I)) was decreased (0.95, 0.80, 0.65, and 0.45 s) relative to simulated T(I) (0.8 s). WOB was measured with a pulmonary mechanics monitor. RESULTS: During VCV-CF and VCV-DF, a V(T) demand of > or = 100% drastically increased WOB, attributable to imposed WOB from the inspiratory valve. Increasing inspiratory flow by using the decelerating flow pattern and/or decreasing T(I) reduced WOB, but generally not to normal levels. "Double-triggered" breaths, with excessive V(T) delivery, often occurred when ventilator T(I) was well below simulated T(I). PCV was most effective in reducing WOB, but V(T) delivery exceeded the LPV target unless T(I) was reduced. CONCLUSIONS: Given our dual goals of reducing both WOB and V(T) during LPV, VCV-DF with relatively brief T(I) appeared to be the best option, followed by PCV with a relatively brief T(I).

Respiratory system mechanics in acute respiratory distress syndrome.

Respiratory mechanics research is important to the advancement of ARDS management. Twenty-eight years ago, research on the effects of PEEP and VT indicated that the lungs of ARDS patients did not behave in a manner consistent with homogenously distributed lung injury. Both Suter and colleagues] and Katz and colleagues reported that oxygenation continued to improve as PEEP increased (suggesting lung recruitment), even though static Crs decreased and dead-space ventilation increased (suggesting concurrent lung overdistension). This research strongly suggested that without VT reduction, the favorable effects of PEEP on lung recruitment are offset by lung overdistension at end-inspiration. The implications of these studies were not fully appreciated at that time, in part because the concept of ventilator-associated lung injury was in its nascent state. Ten years later. Gattinoni and colleagues compared measurements of static pressure-volume curves with FRC and CT scans of the chest in ARDS. They found that although PEEP recruits collapsed (primarily dorsal) lung segments, it simultaneously causes overdistension of non-dependent, inflated lung regions. Furthermore, the specific compliance of the aerated, residually healthy lung tissue is essentially normal. The main implication of these findings is that traditional mechanical ventilation practice was injecting excessive volumes of gas into functionally small lungs. Therefore, the emblematic low static Crs measured in ARDS reflects not only surface tension phenomena and recruitment of collapsed airspaces but also overdistension of the remaining healthy lung. The studies reviewed in this article support the concept that lung injury in ARDS is heterogeneously distributed, with resulting disparate mechanical stresses, and indicate the additional complexity from alterations in chest wall mechanics. Most of these studies, however, were published before lung-protective ventilation. Therefore, further studies are needed to refine the understanding of the mechanical effects of lung-protective ventilation. Although low-VT ventilation is becoming a standard of care for ARDS patients, many issues remain unresolved; among them are the role of PEEP and recruitment maneuvers in either preventing or promoting lung injury and the effects of respiratory rate and graded VT reduction on mechanical stress in the lungs. The authors believe that advances in mechanical ventilation that may further improve patient outcomes are likely to come from more sophisticated monitoring capabilities (ie, the ability to measure P1 or perhaps Cslice) than from the creation of new modes of ventilatory support.

Multivessel beating heart robotic myocardial revascularization increases morbidity and mortality.

OBJECTIVE: The vast majority of reports describing beating heart robotic myocardial revascularization (total endoscopic coronary artery bypass) contain very small numbers of patients undergoing single-vessel bypass. We present a large series of patients undergoing multivessel total endoscopic coronary artery bypass. METHODS: We performed a retrospective clinical review of 106 patients undergoing total endoscopic coronary artery bypass (72% multivessel) at 1 institution by 1 experienced cardiac surgeon/physician assistant team. These results were compared with the expected clinical outcomes from conventional coronary artery bypass grafting calculated using the Society of Thoracic Surgeons risk calculator. RESULTS: Of the 106 patients, 1% underwent quadruple total endoscopic coronary artery bypass, 8% triple, 63% double, and 28% single. The emergent conversion rate for hemodynamic instability was 6.6%. The postoperative renal failure rate (doubling of baseline serum creatinine or dialysis required) was 7.5%. Overall, 23 patients (21.7%) exhibited at least 1 major morbidity/mortality (4 deaths). The number of vessels bypassed (single/double/triple/quadruple) correlated positively with the surgical/operating room time, the lung separation time, vasoactive medication use, blood use, a postoperative ventilation time longer than 24 hours, intensive care unit length of stay, and hospital length of stay. An increased surgical time was significantly associated with major morbidity (P = .011) and mortality (P = .043). A comparison with the Society for Thoracic Surgeons expected outcomes revealed a similar hospital length of stay but an increased incidence of prolonged ventilation (P = .003), renal failure (P < .001), morbidity (P = .045), and mortality (P = .049). CONCLUSIONS: Our results suggest that addressing multivessel coronary artery disease using total endoscopic coronary artery bypass offers no obvious clinical benefits and might increase the morbidity and mortality.

Effects of tidal volume on work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome.

OBJECTIVE: To assess the effects of step-changes in tidal volume on work of breathing during lung-protective ventilation in patients with acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). DESIGN: Prospective, nonconsecutive patients with ALI/ARDS. SETTING: Adult surgical, trauma, and medical intensive care units at a major inner-city, university-affiliated hospital. PATIENTS: Ten patients with ALI/ARDS managed clinically with lung-protective ventilation. INTERVENTIONS: Five patients were ventilated at a progressively smaller tidal volume in 1 mL/kg steps between 8 and 5 mL/kg; five other patients were ventilated at a progressively larger tidal volume from 5 to 8 mL/kg. The volume mode was used with a flow rate of 75 L/min. Minute ventilation was maintained constant at each tidal volume setting. Afterward, patients were placed on continuous positive airway pressure for 1-2 mins to measure their spontaneous tidal volume. MEASUREMENTS AND MAIN RESULTS: Work of breathing and other variables were measured with a pulmonary mechanics monitor (Bicore CP-100). Work of breathing progressively increased (0.86 +/- 0.32, 1.05 +/- 0.40, 1.22 +/- 0.36, and 1.57 +/- 0.43 J/L) at a tidal volume of 8, 7, 6, and 5 mL/kg, respectively. In nine of ten patients there was a strong negative correlation between work of breathing and the ventilator-to-patient tidal volume difference (R = -.75 to -.998). CONCLUSIONS: : The ventilator-delivered tidal volume exerts an independent influence on work of breathing during lung-protective ventilation in patients with ALI/ARDS. Patient work of breathing is inversely related to the difference between the ventilator-delivered tidal volume and patient-generated tidal volume during a brief trial of unassisted breathing.

Piriformis syndrome: anatomic considerations, a new injection technique, and a review of the literature.

BACKGROUND: Piriformis syndrome can be caused by anatomic abnormalities. The treatments of piriformis syndrome include the injection of steroid into the piriformis muscle and near the area of the sciatic nerve. These techniques use either fluoroscopy and muscle electromyography to identify the piriformis muscle or a nerve stimulator to stimulate the sciatic nerve. METHODS: The authors performed a cadaver study and noted anatomic variations of the piriformis muscle and sciatic nerve. To standardize their technique of injection, they also noted the distance from the lower border of the sacroiliac joint (SIJ) to the sciatic nerve. They retrospectively reviewed the charts of 19 patients who had received piriformis muscle injections, noting the site of needle insertion in terms of the distance from the lower border of the SIJ and the depth of needle insertion at which the motor response of the foot was elicited. The authors tabulated the response of the patients to the injection, any associated diagnoses, and previous treatments that these patients had before the injection. Finally, they reviewed the literature on piriformis syndrome, a rare cause of buttock pain and sciatica. RESULTS: In the cadavers, the distance from the lower border of the SIJ to the sciatic nerve was 2.9 +/- 0.6 (1.8-3.7) cm laterally and 0.7 +/- 0.7 (0.0-2.5) cm caudally. In 65 specimens, the sciatic nerve passed anterior and inferior to the piriformis. In one specimen, the muscle was bipartite and the two components of the sciatic nerve were separate, with the tibial nerve passing below the piriformis and the peroneal nerve passing between the two components of the muscle. In the patients who received the injections, the site of needle insertion was 1.5 +/- 0.8 (0.4-3.0) cm lateral and 1.2 +/- 0.6 (0.5-2.0) cm caudal to the lower border of the SIJ as seen on fluoroscopy. The needle was inserted at a depth of 9.2 +/- 1.5 (7.5-13.0) cm to stimulate the sciatic nerve. Patients had comorbid etiologies including herniated disc, failed back surgery syndrome, spinal stenosis, facet syndrome, SIJ dysfunction, and complex regional pain syndrome. Sixteen of the 19 patients responded to the injection, their improvements ranged from a few hours to 3 months. CONCLUSIONS: Anatomic abnormalities causing piriformis syndrome are rare. The technique used in the current study was successful in injecting the medications near the area of the sciatic nerve and into the piriformis muscle.

Contralateral tension pneumothorax during one-lung ventilation for lobectomy: diagnosis aided by fiberoptic bronchoscopy.

IMPLICATIONS: Tension pneumothorax during one-lung ventilation can be a life threatening emergency. Clinical diagnosis may be confusing in the operative setting. We present a case in which fiberoptic bronchoscopy excluded tube malpositioning and lead us to the diagnosis of a tension pneumothorax.