Association between traumatic brain injuries and ketamine infusion side effects following combat injury.

INTRODUCTION: Ketamine is a vital component for acute pain management in emergency trauma care for both civilian and military hospitals. This preliminary analysis examined whether combat-injured US service members sustaining traumatic brain injuries (TBI) experienced increased odds of ketamine side effects compared with those without TBI. METHODS: This preliminary analysis included combat-injured service members, ages ≥18 years with documented pain scores during the 24 hours before and 48 hours after receiving an intravenous ketamine infusion at Walter Reed National Military Medical Center (WRNMMC) between 2007 and 2014. Logistic regression modeling examined the association between TBI and ketamine side effects (eg, hallucinations, nightmares, dysphoria, nausea, decreased oxygen saturation) during hospitalisation. RESULTS: Of the 77 patients, 62% presented with a documented TBI. Side effects were documented for 18.8% of those without TBI and 24.4% of those with TBI. Analyses were unable to find evidence against the null hypothesis with the current sample size, even when adjusting for injury characteristics and preinfusion opioid doses (adjusted OR=0.90 (95% CI 0.26 to 3.34), p=0.87). CONCLUSION: In this small sample of combat-injured service members, we were unable to detect a difference in ketamine-related side effects by documented TBI status. These hypothesis-generating findings support the need for future studies to examine the use of intravenous ketamine infusions for pain management, and subsequent care outcomes in patients who experience polytraumatic trauma inclusive of TBI.

Safety and Tolerability of Thrombin Inhibition in Scleroderma-Associated Interstitial Lung Disease.

OBJECTIVE: Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) (scleroderma) and the leading cause of scleroderma-related deaths. There exists an unmet need for a new drug therapy for ILD-complicated SSc. Substantial evidence supports an important role for thrombin in the pathogenesis of SSc-associated ILD (hereafter SSc-ILD), and targeting thrombin with a direct thrombin inhibitor could prove to be a novel and effective treatment strategy. As a first step toward designing a clinical trial to test the efficacy of thrombin inhibition in SSc-ILD, we conducted this study to test the safety and tolerability of dabigatran in patients with SSc-ILD. METHODS: We performed a prospective, single-center, open-label treatment trial with the direct thrombin inhibitor, dabigatran, in patients with SSc-ILD. Any patient with a history of gastrointestinal hemorrhage or gastric antral vascular ectasia was excluded. Blood monitoring was performed monthly, and patient-reported outcomes, pulmonary function tests, and skin scores were obtained at baseline and at 3- and 6-month visits. Bronchoscopy with bronchoalveolar lavage (BAL) was performed at baseline and at 6 months for measurement of lung thrombin activity. RESULTS: Of 15 patients with SSc-ILD, 14 completed 6 months of treatment with dabigatran at 75 mg taken orally twice daily. Adverse events were uncommon and usually mild or unrelated to the study medication. No serious adverse event was observed. Dabigatran was well tolerated, and we observed no significant gastrointestinal, pulmonary, or other safety issues or intolerability. BAL fluid thrombin activity decreased or remained stable in 13 of 14 (92.8%) subjects. CONCLUSION: Dabigatran appears to be safe and well tolerated in patients with SSc-ILD. A larger randomized controlled trial to test the efficacy of direct thrombin inhibition with dabigatran can be considered.

Ambrisentan for sarcoidosis associated pulmonary hypertension.

BACKGROUND: Sarcoidosis associated pulmonary hypertension (SAPH) is associated with significant morbidity and mortality. There is a paucity of information concerning therapy for this condition. METHODS: We performed a prospective, open-label, proof of concept trial of ambrisentan for SAPH. 21 subjects with SAPH received 5 mg/day of ambrisentan for 4 weeks and then 10/mg day for 20 subsequent weeks. RESULTS: No significant change was noted in the 6-minute walk distance over the course of the study (mean change between week 0 and 24: 9.8 +/- 54.6 meters, p: NS). There were also no significant differences between weeks 0 and 24 in terms of dyspnea as measured by the modified Borg scale, serum brain naturetic peptide, diffusing capacity, and quality of life as measured by the Short Form-36. There was a high dropout rate: overall: 11/21, 52%; social reasons: 3/21, 14%; medical reasons: 8/21, 38% because of dyspnea: 6/21, 29% and/or edema: 4/21, 19%. Of those who completed the 24 week study (10/21, 48%), there was an improvement in their WHO functional class and a marked improvement in their health related quality of life as measured by the St. George Respiratory questionnaire (-15.3 +/- 25.0). However both these improvments did not reach statistical significance possibly because of the small sample size. CONCLUSION: Although ambrisentan was not well tolerated by many of these subjects with SAPH, in those who remained in this 24-week trial, improvements in WHO functional class and in health related quality of life suggested a possible benefit of this drug in selected patients.

Fundoplication eliminates chronic cough due to non-acid reflux identified by impedance pH monitoring.

The symptoms of extra-oesophageal gastro-oesophageal reflux disease (GORD) (such as chronic cough and hoarseness) are traditionally more difficult to treat than typical GORD symptoms (heartburn and regurgitation). Patients with extra-oesophageal manifestations may require longer and higher doses of acid suppressive therapy. In patients not responding to acid suppressive therapy the physician faces a dilemma as to whether the symptoms are due to ongoing acid reflux, non-acid reflux, or not associated with reflux. We report the case of a 45 year old woman with a history of a chronic cough referred for fundoplication after documenting her symptoms were associated with non-acid reflux using multichannel intraluminal impedance and pH (MII-pH).

Is there an anatomic explanation for chest pain in patients with pulmonary sarcoidosis?

BACKGROUND: Chest pain (CP), its cause unknown, is a common and often prominent symptom of sarcoidosis. METHODS: We determined the frequency and character of CP in patients with pulmonary sarcoidosis and examined its relationship with (1) length of time since diagnosis, (2) roentgenograhic stage, and (3) radiographic abnormalities on spiral chest computed tomography (CT). RESULTS: Twenty-two patients were studied: 14 of 22 patients (64%) had CP, with 4 of 14 (29%) identifying pain as their primary symptom. Eleven of 14 (79%) had pleuritic CP; 12 of 22 (54.5%) described CP as substernal; and 5 of 22 (22.7%) described CP between the scapula. There was not a significant correlation between CP and the presence or degree of lymphadenopathy. There was no significant correlation between CP and the presence or location of pleural disease. Abnormalities of other thoracic structures also had no significant correlation with the presence of CP. CONCLUSIONS: We conclude that there is no "anatomic reason" for CP in patients with pulmonary sarcoidosis that is evident on chest CT.