Anthony Passannante

Liver allograft antibody‐mediated rejection with demonstration of sinusoidal C4d staining and circulating donor‐specific antibodies

The importance of antibody‐mediated rejection (AMR) in ABO‐compatible liver transplantation is controversial. Here we report a prospective series of liver recipients with a preoperative positive crossmatch. To establish the diagnosis of AMR in liver recipients, the criteria described for kidney allografts were adopted. In approximately 10% of 197 liver transplants, we observed a positive T and B cell flow crossmatch before transplantation. Fifteen of 19 patients converted to negative crossmatches early after transplantation and displayed normal liver function while they were on routine immunosuppression. Four patients maintained positive crossmatches. Three of the 4 met the criteria for AMR and showed evidence of graft dysfunction, the presence of donor‐specific antibodies (DSAs), morphological tissue destruction with positive C4d linear staining on the graft sinusoidal endothelium, and improved function with attempts to eliminate DSAs. A persistently positive crossmatch after liver transplantation may lead to early, severe AMR and liver failure. C4d staining in the liver sinusoidal endothelium should alert one to the possibility of AMR. In our experience, patients with a positive crossmatch should have it repeated at 2 weeks and, if it is positive, again at 3 to 5 weeks. Recipients with an unknown preoperative crossmatch who develop early cholestasis of unclear etiology should be crossmatched or tested for the presence of DSAs to evaluate for AMR. Liver Transpl, 2011.

Spinal Anesthesia and Permanent Neurologic Deficit After Interscalene Block

Case Report A 53-yr-old male with a history of depression and right rotator cuff disruption underwent uncomplicated right shoulder reconstruction under general anesthesia. For postoperative pain relief, an interscalene block performed after the surgical procedure, but before terminating general anesthesia, was planned. Preoperative neurologic examination was normal. With the patient tracheally intubated and anesthetized with 0.4% isoflurane (end-tidal) and 50% nitrous oxide, the right neck was prepared and draped. A 3-in., 24-gauge, B-bevel insulated nerve stimulator needle was used to locate the brachial plexus in the interscalene groove at the level of C-6. The needle was directed in a caudal and posterior direction. Motor response in the hand was obtained with 0.2-mA current at a depth of 1 in. No cerebrospinal fluid or blood could be aspirated. A mixture of 0.25% bupivicaine, 20 mL, with epinephrine 1:200,000 was administered in 5 mL aliquots. Isoflurane and nitrous oxide were discontinued. Five minutes after injection, arterial blood pressure was 70/40 mm Hg, and the patient’s pupils were fixed and widely dilated. Subarachnoid injection was presumed. Arterial blood pressure was supported with the administration of ephedrine, phenylephrine, and intravenous fluid and the endotracheal tube left in place. The patient was presumed to be conscious and unable to move; thus, midazolam was administered to ensure sedation and amnesia until motor function returned. The subarachnoid block lasted for 150 min, after which the patient was extubated. Neurologic examination was normal, except for dense sensory and motor block of the right arm. Electromyography performed 5 mo after the procedure showed increased insertional activity, positive sharp waves, and fibrillation potentials in muscles innervated by the medial cord, consistent with a brachial plexopathy with severe involvement of the medial cord. The nerve to the infraspinatus muscle was also involved, and there was evidence of

Midazolam amnesia and dual-process models of the word-frequency mirror effect

The word-frequency mirror effect (Glanzer & Adams, 1985) is the finding that subjects are more accurate on low frequency words than high frequency words for old and new items in recognition memory. Recently, several theorists (Guttentag & Carroll, 1997; Joordens & Hockley, 2000; Reder et al., 2000) have proposed dual-process accounts of the word-frequency mirror effect. These accounts hypothesize that the low frequency advantage on old items arises from increased recollection of these items, while the low frequency advantage on new items arises from reduced familiarity of these items. We tested these views using midazolam amnesia. Midazolam is a safe, fast-acting benzodiazepine that produces a dense anterograde amnesia. Based on the hypothesis that midazolam amnesia should have larger effects on recollection than familiarity, we predicted that: (1) old high frequency words should have an advantage over old low frequency words in a midazolam condition (i.e., the traditional effect should reverse); and (2) the traditional advantage of new low frequency words over new high frequency words should replicate in a midazolam condition. Both predictions of the dual-process approach were confirmed. Additional analyses demonstrated that a single-process signal detection model could not account for the current results and that midazolam amnesia produces a larger effect on recollection processes than on familiarity processes.

Midazolam amnesia and conceptual processing in implicit memory

Prominent theories of implicit memory (D. Schacter, B. Church, & J. Treadwell, 1994) emphasize the dominant role of perceptual processing in mediating priming on perceptual implicit memory tests. Examinations of the effects of conceptual processing on perceptual implicit memory tests have produced ambiguous results. Although a number of investigations (e.g., J. Toth & R. Hunt, 1990) have demonstrated that variations in conceptual processing affect priming on perceptual implicit memory tests, these effects may arise because of the contaminating effects of explicit memory. The current experiment examined this controversy using midazolam, a benzodiazepine that produces a dense, albeit temporary, anterograde amnesia when injected prior to study. The experiment examined whether the effects of generation found on the implicit memory test of perceptual identification were affected by a midazolam injection prior to study. Results demonstrated that midazolam substantially diminished generation effects in free and cued recall, as well as overall performance on these tests, but had no detectable effect on the generation effect in perceptual identification.

Preoperative assessment: pulmonary

Understanding the risk factors for the development of PPCs allows targeted interventions aimed at reducing the frequency and severity of PPCs. The broad categories of what increases the likelihood of developing a PPC are understood but specific understanding of how individual risk factors act to cause PPCs is lacking,and there is little information regarding the interaction or synergy between risk factors. Further research is needed to define the nature of risk factors and develop better predictive models of patients at risk for developing PPCs. It is clear that anesthetic agents produce significant changes in the respiratory system but further information is needed to define how such changes contribute, if at all, to the subsequent development of PPCs. The ongoing controversy regarding the value of regional analgesia or anesthetic techniques, especially epidural analgesia and anesthesia, in reducing or preventing PPCs requires well-done randomized clinical trials. Further research is also needed in the area of postoperative care such as interventions in patients with OSA or the use of inventive spirometric techniques.

The effect of midazolam on implicit memory tests

Substantial empirical evidence exists suggesting that there are distinct forms of explicit and implicit memory. However, methodological problems have hampered attempts to identify the nature of the information processing underlying these forms of memory. These problems include the contamination of performance on implicit memory tests by explicit memory processes, as well as a host of difficulties inherent in correlational approaches that involve amnesiac subjects. In this paper we attempt to explore whether midazolam, a benzodiazepine used in surgical anesthesia, might be useful for studying implicit memory. Specifically, we attempt to determine whether midazolam produces selective effects on explicit, as opposed to implicit, memory. We focus on midazolam because of prior studies demonstrating that benzodiazepines do not affect implicit memory and because its rapid pharmacokinetics ensure that sedative effects are minimized when testing occurs at relatively short retention intervals. The results of an experiment using free recall, fragment completion and perceptual identification tests suggest that midazolam diminishes memory in implicit and explicit memory tests, although the diminution is proportionally larger in explicit memory. These results constrain the inferences that may be drawn when midazolam is used to explore implicit memory.

The effect of midazolam on implicit and explicit memory in category exemplar production and category cued recall

Transfer‐appropriate processing theory (Roediger, Weldon, & Challis, 1989) proposes that dissociations between performance on explicit and implicit memory tests arise because these tests often rely on different types of information processing (e.g., perceptual processing vs conceptual processing). This perspective predicts that implicit and explicit memory tasks that rely primarily on conceptual processing should show comparable results, not dissociations. Numerous studies have demonstrated such similarities. It is, however, possible that these results arise from explicit memory contamination of performance on implicit memory tasks. To address this issue, an experiment was conducted in which participants were administered the sedative midazolam prior to study. Midazolam is known to create a temporary, but dense, period of anterograde amnesia. The effects of blocking stimulus materials by semantic category at study and generation at study were investigated on category exemplar production and category‐cued recall. The results of this study demonstrated a dissociation of the effects of midazolam on category exemplar production and category‐cued recall. Specifically, midazolam reduced the effect of blocking stimulus materials in category‐cued recall, but not in category exemplar production. The differential effect of midazolam on explicit and implicit memory is at odds with transfer‐appropriate processing theory and suggests that theories of memory must distinguish the roles of different types of conceptual processing on implicit and explicit memory tests.

Midazolam amnesia and short-term/working memory processes

We examined whether midazolam impairs short-term/working memory processes. We hypothesize that prior dissociations in midazolams effects on short-term/working memory tasks and episodic memory tasks arise because midazolam has a larger effect on episodic memory processes than on short-term/working memory processes. To examine these issues, .03 mg/kg of participants bodyweight of midazolam was administered in a double-blind placebo-controlled within-participant design. Performance on the digit span and category generation/recall tasks was examined. The results of Experiment 1 demonstrated that: (1) midazolam impaired performance on the digit span task; (2) midazolam did not impair performance on the category generation task; (3) midazolam impaired performance on the category recall task; and (4) midazolams effect on category recall was four times as large as its effect on digit span. The results of Experiment 2 demonstrated that midazolam did not impair digit span performance when the digit span task was administered at a later time. These results suggest that midazolam can impair short-term/working memory processes, but these effects are substantially smaller than midazolams effect on episodic memory processes. Moreover, they demonstrate that conscious awareness of materials during study is not sufficient to produce episodic memory.

Alteration of renal blood flow during epidural anesthesia in normal subjects

The cardiovascular consequences of epidural anesthesia secondary to sympathetic blockade are well documented; however, their repercussions on renal hemodynamics in humans have not been reported.We investigated the effect of epidural anesthesia on renal blood flow (RBF) in 13 healthy volunteers 18-45 yr of age. RBF was measured using paraaminohippurate clearance before and after bilateral T6 epidural sensory block (to ensure adequate sympathetic renal nerve blockade). Fpidural anesthesia was established using 22 +/- 3 mL of 2% plain lidocaine (without epinephrine) via L1-L2 epidural catheter; urine output was measured using a three-way Foley catheter. Mean arterial pressure remained >or=to70 mm Hg in all subjects without any pharmacologic intervention. Mean RBF before epidural anesthesia was 16.1 +/- 6.8 mL [centered dot] kg-1 [centered dot] min-1 and 14.3 +/- 2.9 ml [centered dot] kg-1 [centered dot] min-1 after bilateral T6 epidural blockade. We conclude that the institution of epidural anesthesia in healthy subjects does not result in a significant change in RBF (P > 0.25). (Anesth Analg 1997;84:1076-80)

Anesthetic Management of Patients with Obesity with and Without Sleep Apnea

The global obesity epidemic presents anesthesia providers with unique and complex challenges as an increasing number of patients with elevated body mass index present for medical care. Pharmacokinetics, respiratory and cardiac physiology, positioning, regional anesthetic techniques, monitoring, and postoperative care are all profoundly affected by increased body mass. In recent years, the occult impact of undiagnosed obstructive sleep apnea on perioperative morbidity and mortality has marshaled increased attention from both patients and practitioners. A summary and discussion of the Practice Guidelines developed by the American Society of Anesthesiologists regarding the care of patients with obstructive sleep apnea is provided.