Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury

Acute respiratory distress syndrome (ARDS) usually requires symptomatic supportive therapy by intubation and mechanical ventilation with the supplemental use of high oxygen concentrations. Although oxygen therapy represents a life-saving measure, the recent discovery of a critical tissue-protecting mechanism predicts that administration of oxygen to ARDS patients with uncontrolled pulmonary inflammation also may have dangerous side effects. Oxygenation may weaken the local tissue hypoxia-driven and adenosine A2A receptor (A2AR)-mediated anti-inflammatory mechanism and thereby further exacerbate lung injury. Here we report experiments with wild-type and adenosine A2AR-deficient mice that confirm the predicted effects of oxygen. These results also suggest the possibility of iatrogenic exacerbation of acute lung injury upon oxygen administration due to the oxygenation-associated elimination of A2AR-mediated lung tissue-protecting pathway. We show that this potential complication of clinically widely used oxygenation procedures could be completely prevented by intratracheal injection of a selective A2AR agonist to compensate for the oxygenation-related loss of the lung tissue-protecting endogenous adenosine. The identification of a major iatrogenic complication of oxygen therapy in conditions of acute lung inflammation attracts attention to the need for clinical and epidemiological studies of ARDS patients who require oxygen therapy. It is proposed that oxygen therapy in patients with ARDS and other causes of lung inflammation should be combined with anti-inflammatory measures, e.g., with inhalative application of A2AR agonists. The reported observations may also answer the long-standing question as to why the lungs are the most susceptible to inflammatory injury and why lung failure usually precedes multiple organ failure

Digital Subtraction Angiography Versus RealTime Fluoroscopy for Detection of Intravascular Penetration Prior to Epidural Steroid Injections: Meta-Analysis of Prospective Studies

Background: Neurological injury is a rare but devastating complication of epidural steroid injections (ESIs) generally thought to arise from neurovascular compromise. The use of real-time fluoroscopy (RTF) with contrast media is the most common preventative measure taken to avoid intravascular penetration. In 2002, it was proposed that digital subtraction angiography (DSA) might be more useful than RTF. Since then, several prospective studies have advocated for its use. Objectives: As DSA is not currently a “gold standard,” a meta-analysis was performed to compare the efficacy of DSA versus RTF for detection of intravascular penetration during ESI. Study Design: Meta-analysis of prospective observational studies. Methods: A targeted Pubmed search was conducted, yielding 49 reports and 4 manuscripts, which were analyzed using Review Manager Software (Rev Man 5.2). Inclusion/exclusion criteria: peer-reviewed prospective reports comparing the sensitivity of DSA to RTF in the same individuals without change in needle position between comparative imaging. Pooled estimate of odds ratios with 95% confidence interval using a random effect model was applied. Results: There were a total of 188 intravascular events from 1,290 ESIs performed. RTF was able to detect 148 events with DSA detecting an additional 40 events missed by RTF. No major neurological complications were reported. DSA had a statistically significant favorable odds ratio over RTF for detection of intravascular penetration during ESI (OR = 1.32 [1.05 – 1.67]; P = 0.02). Limitations: Although the major methodological aspects of each study assessed in this metaanalysis were quite similar, there were small differences in needle gauge and the selection of secondary outcome measures. Despite attempts to minimize it, concern for operator bias also exists. Conclusions: DSA had a 32% improvement (OR = 1.32) for detection of intravascular penetration with ESI when compared to RTF. Although this supports advocacy for use of DSA, it also suggests that there is a greater than 30% “missed-events” rate for detection of vascular penetration when using RTF for ESI, which does not correlate with the generally reported cumulative rates of complications (1%). This discrepancy suggests that factors other than vascular events also play a role in complications. Nonetheless, given the evidence, we advocate for the increased use of DSA over RTF for transformational ESIs. Key words: Digital subtraction angiography, real-time fluoroscopy, epidural steroid injection, complications, outcomes, pain imaging, chronic pain, intravascular injection, meta-analysis</jats:p

Adjuvant Hyaluronidase to Epidural Steroid Improves the Quality of Analgesia in Failed Back Surgery Syndrome: A Prospective Randomized Clinical Trial

Background: Management of low back pain after spinal surgeries is one of the most challenging problems in pain medicine. Transforaminal lumbar epidural steroid injection has been used with inconsistent response. Most patients require multiple and frequent injections due to high recurrence of back pain. Objective: To find out whether the addition of hyaluronidase to the epidural injectate affects the quality and duration of analgesia in patients with low back pain secondary to failed back surgery syndrome. Study Design: Prospective randomized trial. Methods: The study was registered in the Government Clinical Trial registry and the protocol was reviewed and approved by the institutional review board. After obtaining an informed consent, 25 patients with low back pain due to failed back syndrome were randomly assigned to receive a transforaminal epidural injection of hyaluronidase 1500 IU (HYL) or normal saline (NSL) to a mixture of bupivacaine 0.5% (1 mL) and triamcinolone 40mg (1 mL) in a doubleblind fashion. An interventional pain specialist using fluoroscopic guidance performed all epidural injections. The patients received a comprehensive neurological examination by a non-interventional pain specialist who was blinded to the treatment during their follow-up visits, scheduled one, 2, and 4 weeks after the intervention. Numerical pain scores, analgesic requirement, and satisfaction scores were recorded during every visit. Results: There was no difference in demographic data between the 2 groups. Pain scores and total analgesic requirement were significantly lower in the HYL group at 2 and 4 weeks after blockade (P &lt; 0.01). Patient satisfaction was higher in the HYL group. Limitations: The study was limited by a relatively small sample size. Conclusion: We conclude that adding hyaluronidase to the epidural injectate was effective in the management of chronic low back pain in patients with failed back surgery syndrome demonstrated over a period of 4 weeks. Key words: Low back pain, lumbar epidural injection, steroid, hyalorunidase, bupivacaine</jats:p