A rare case of renal infarction due to heroin and amphetamine abuse: case report.

BACKGROUND: Renal infarctions as a result of recreational drug use are rare and are commonly associated with cocaine use. Although amphetamines have a similar mechanism of action as cocaine, there are few reports linking them to ischemic events, and only one to renal infarction. Similarly, few reports link heroin use with infarcts, but never in the kidney. Although uncommon, several mechanisms have been implicated in heroin and amphetamine-induced infarction, including vasculopathy, vasculitis and the activation of the coagulation cascade. CASE PRESENTATION: 47-year-old female with a past medical history of non-intravenous heroin and amphetamine abuse, chronic obstructive pulmonary disease, hypertension, hyperlipidemia presented with right lower extremity swelling and rash, which was diagnosed as cellulitis and treated appropriately. Incidentally, the patient was found to have an acute kidney injury and further workup identified multiple renal infarcts in the right kidney. The patient had no past medical history of clotting disorders. Blood culture and urine cultures were sterile; autoimmune and hypercoagulable workup were negative. Urinalysis was unremarkable. Urine toxicology was only positive for opiates and amphetamines, which were thought to be the most likely cause of the renal infarct. Patient was lost to outpatient follow up due to noncompliance, but returned to the hospital for re-emergence of her cellulitis, during which no new infarcts were discovered, and the previous renal infarct had scarred over. CONCLUSION: There are very few reports of heroin and amphetamine-induced infarctions. This case report describes a rare but important complication of heroin/amphetamine abuse that could be easily overlooked.

A pilot study showing that repeated exposure to stress produces alterations in subsequent responses to anesthetics in rats.

The repeated use of a drug frequently leads to alterations in the response to that drug. We undertook this study to determine whether multiple exposures to the general anesthetic produced alterations in subsequent exposures to this anesthetic. For this study, adult male rats were anesthetized with 2.5% isoflurane for one hour. The rats were divided into 4 groups of 8 rats each. Groups 1-3 were transported between their homeroom and the anesthesia testing room and were handled in an identical manner weekly for a period of 12 weeks, but were anesthetized on different schedules. Group 1 was anesthetized weekly for 12 weeks, Group 2 on either a 3 or 4 week schedule and Group 3 was anesthetized a single time, at the end of the 12 week period. To receive anesthesia multiple times, animals were transported from their homeroom to the anesthesia location and handled repeatedly. We took into consideration of the frequency of anesthesia exposure and the stress involved. Rats in groups 2 and 3 were placed in the anesthesia chamber, with O2 but with no anesthetic, every week when they were not scheduled to receive anesthesia. In Group 4, rats were not transported or handled in any way and stayed in the home room for a period of 12 weeks. Rats in this group were anesthetized once, at the very end of the study. Recovery of the rat's righting reflex was used to assess the acceleration of recovery time from general anesthesia. Group 1 rats showed dramatically faster emergence from anesthesia after several rounds of anesthesia. Surprisingly, Groups 2 and 3 rats, treated in an identical manner as Group 1, but which were anesthetized on different schedules, also exhibited more rapid emergence from anesthesia, when compared to Group 4 rats, which were never handled or transported prior to a single anesthesia. These results suggest that the stress of transportation and handling altered responsiveness to anesthesia. Our results show that responsiveness to anesthetic agents can change over time outside of the normal developmental changes taking place in rats as they age.

Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: There are currently no drugs clinically available to reverse general anesthesia. We previously reported that caffeine is able to accelerate emergence from anesthesia in rodents. This study was carried out to test the hypothesis that caffeine accelerates emergence from anesthesia in humans. METHODS: We conducted a single-center, randomized, double-blind crossover study with eight healthy males. Each subject was anesthetized twice with 1.2% isoflurane for 1 h. During the final 10 min of each session, participants received an IV infusion of either caffeine citrate (15 mg/kg, equivalent to 7.5 mg/kg of caffeine base) or saline placebo. The primary outcome was the average difference in time to emergence after isoflurane discontinuation between caffeine and saline sessions. Secondary outcomes included the end-tidal isoflurane concentration at emergence, vital signs, and Bispectral Index values measured throughout anesthesia and emergence. Additional endpoints related to data gathered from postanesthesia psychomotor testing. RESULTS: All randomized participants were included in the analysis. The mean time to emergence with saline was 16.5 ± 3.9 (SD) min compared to 9.6 ± 5.1 (SD) min with caffeine (P = 0.002), a difference of 6.9 min (99% CI, 1.8 to 12), a 42% reduction. Participants emerged at a higher expired isoflurane concentration, manifested more rapid return to baseline Bispectral Index values, and were able to participate in psychomotor testing sooner when receiving caffeine. There were no statistically significant differences in vital signs with caffeine administration and caffeine-related adverse events. CONCLUSIONS: Intravenous caffeine is able to accelerate emergence from isoflurane anesthesia in healthy males without any apparent adverse effects.

Caffeine accelerates recovery from general anesthesia via multiple pathways.

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP]i)-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A2A receptor blockade and [cAMP]i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP]i and adenosine receptor blockade play a role in this response.NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia.