Allan Gottschalk

Sedation Depth During Spinal Anesthesia and the Development of Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Repair

OBJECTIVE To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium. PATIENTS AND METHODS We performed a double-blind, randomized controlled trial at an academic medical center of elderly patients (>or=65 years) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation. Sedation depth was titrated using processed electroencephalography with the bispectral index (BIS), and patients were randomized to receive either deep (BIS, approximately 50) or light (BIS, >or=80) sedation. Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery. RESULTS From April 2, 2005, through October 30, 2008, a total of 114 patients were randomized. The prevalence of postoperative delirium was significantly lower in the light sedation group (11/57 [19%] vs 23/57 [40%] in the deep sedation group; P=.02), indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation. The mean +/- SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group (0.5+/-1.5 days vs 1.4+/-4.0 days; P=.01). CONCLUSION The use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted.

Preventing and Treating Pain after Thoracic Surgery

THE pain that accompanies thoracic surgery is notable for its intensity and duration. Acutely, moderate to severe levels of pain may not decrease substantially over the course of hospitalization and the first postoperative month. Chronically, pain can last for months to years, and even low levels of pain can decrease function. Other than pain syndromes associated with limb amputation, pain after thoracic surgery may be the most recognized pain syndrome associated with a specific surgery. Although used with increasing frequency, thoracoscopic approaches have not had the favorable impact on pain that many had anticipated. Given that the adverse effects of thoracic surgery on pulmonary function can be mitigated by effective perioperative analgesia, it is not surprising that thoracic surgeons have joined anesthesiologists in becoming strong advocates of analgesic interventions known to limit the pain accompanying thoracic surgery. Here, we review evidence-based strategies for preventing and treating this type of pain.

LONG-TERM PAIN AND ACTIVITY DURING RECOVERY FROM MAJOR THORACOTOMY USING THORACIC EPIDURAL ANALGESIA

Background Pain following thoracotomy can persist for years with an undetermined impact on quality of life. Factors hypothesized to modulate this painful experience include analgesic regimen, gender, and type of incision. Methods A total of 157 generally healthy patients of both genders scheduled for segmentectomy, lobectomy, or bilobectomy through a posterolateral or muscle-sparing incision were randomly assigned to receive thoracic epidural analgesia initiated prior to incision or at the time of rib approximation. Pain and activity scores were obtained 4, 8, 12, 24, 36, and 48 weeks after surgery. Results Overall, there were no differences in pain scores between the control and intervention groups during hospitalization (P ≥ 0.165) or after discharge (P ≥ 0.098). The number of patients reporting pain 1 yr following surgery (18 of 85; 21.2%) was not significantly different (P = 0.122) from the number reporting preoperative pain (15 of 120; 12.5%). During hospitalization, women reported greater pain than men (worst pain, P = 0.007; average pain, P = 0.016). Women experienced fewer supraventricular tachydysrhythmias (P = 0.013) and were thus discharged earlier (P = 0.002). After discharge women continued to report greater discomfort than men (P ≤ 0.016), but did not differ from men in their level of physical activity (P = 0.241). Conclusions Initiation of thoracic epidural analgesia prior to incision or the use of a muscle-sparing incision did not significantly impact pain or physical activity. Although women reported significantly greater pain during hospitalization and after discharge, they experienced fewer complications, were more likely to be discharged from the hospital sooner, and were just as active after discharge as men.

Predisposing factors for postoperative delirium after hip fracture repair in individuals with and without dementia.

Based on a multifactorial model of delirium, to compare the types and magnitude of pre‐ and intraoperative predisposing factors for incident delirium in a stratified sample of individuals with and without preoperative dementia undergoing acute hip fracture repair.

The glycosylation state of Kv1.2 potassium channels affects trafficking, gating, and simulated action potentials.

We presented evidence previously that decreasing the glycosylation state of the Kv1.1 potassium channel modified its gating by a combined surface potential and a cooperative subunit interaction mechanism and these effects modified simulated action potentials. Here we continued to test the hypothesis that glycosylation affects channel function in a predictable fashion by increasing and decreasing the glycosylation state of Kv1.2 channels. Compared with Kv1.2, increasing the glycosylation state shifted the V(1/2) negatively with a steeper G-V slope, increased activation kinetics with little change in deactivation kinetics or in their voltage-dependence, and decreased the apparent level of C-type inactivation. Decreasing the glycosylation state had essentially the opposite effects and shifted the V(1/2) positively with a shallower G-V slope, decreased activation kinetics (and voltage-dependence), decreased deactivation kinetics, and increased the apparent level of C-type inactivation. Single channel conductance was not affected by the different glycosylation states of Kv1.2 tested here. Hyperpolarized or depolarized shifts in V(1/2) from wild type were apparently due to an increased or decreased level of channel sialylation, respectively. Data and modeling suggested that the changes in activation properties were mostly predictable within and between channels and were consistent with a surface potential mechanism, but those on deactivation properties were not predictable and were more consistent with a conformational mechanism. Moreover the effect on the deactivation process appeared to be channel-type dependent as well as glycosylation-site dependent. The glycosylation state of Kv1.2 also affected action potentials in simulations. In addition, preventing N-glycosylation decreased cell surface Kv1.2 expression levels by approximately 40% primarily by increasing partial endoplasmic reticulum retention and this effect was completely rescued by Kv1.4 subunits, which are glycosylated, but not by cytoplasmic Kvbeta2.1 subunits. The nonglycosylated Kv1.2 protein had a similar protein half-life as the glycosylated protein and appeared to be folded properly. Thus altering the native Kv1.2 glycosylation state affected its trafficking, gating, and simulated action potentials. Differential glycosylation of ion channels could be used by excitable cells to modify cell signaling.

What is the role of NSAIDs in pre-emptive analgesia?

NSAIDs inhibit the cyclo-oxygenase enzymes, and decrease peripheral and central prostaglandin production. In addition to reducing the inflammation that accompanies tissue injury, decreasing prostaglandin production attenuates the response of the peripheral and central components of the nervous system to noxious stimuli. Such a reduction in the response to pain can reduce the peripheral and central sensitisation induced by noxious stimuli, and reduce the pain experienced in response to subsequent noxious stimuli. These properties would seem to make NSAIDs ideal drugs to use in a pre-emptive fashion, where analgesics are administered prior to a noxious stimulus, such as surgery, with the expectation that reduction in peripheral and central sensitisation will lead to a decrease of pain.However, the available perioperative trials of pre-emptive NSAID use have yielded modest or equivocal results, and these may be due, in part, to controversy associated with the definition of pre-emptive analgesia and how to conduct the corresponding clinical trials. Although NSAIDs may have a limited ability by themselves to induce a pre-emptive analgesic effect, the available trials suggest how the perioperative use of these drugs may be made more effective. It is expected that NSAIDs will play an increasing role in multimodal analgesia and pain relief in general.

Postoperative Opioid Consumption and Its Relationship to Cognitive Function in Older Adults with Hip Fracture

To determine the relationship between opioid consumption and cognitive impairment after hip fracture repair.

Clinical and Demographic Characteristics of Patients With Chronic Pain After Major Thoracotomy

ObjectivesThe characteristics and etiology of long-term pain after major thoracotomy and methods for its prevention have yet to be established. MethodsOne hundred and twenty patients who had completed the hospital-based portion of a prior study to evaluate the efficacy of intraoperative epidural use during major thoracotomy, all of whom had received patient-controlled thoracic epidural analgesia until at least thoracostomy tube removal, and who were followed for 48 weeks after surgery provided data for this study. ResultsAlthough preoperative pain was associated with elevated pain levels during hospitalization and the first few months after discharge, there was no association with pain 48 weeks after surgery. Furthermore, pain during the first few postoperative days, although associated with pain during the first few postoperative months, was not associated with pain 48 weeks after surgery. However, for patients who reported pain 48 weeks after surgery, pain levels were elevated late in hospitalization after epidural catheter removal and pain after discharge did not decrease over time. During hospitalization, patients who would eventually report pain 48 weeks after surgery experienced a greater impact of pain and reported that analgesic therapy was less effective. DiscussionPostoperative pain that persists but eventually dissipates was a common finding whose intensity was associated with immediate preoperative and postoperative pain levels. In contrast, pain later on during hospitalization, its impact, and perceived analgesic effectiveness best identified those who would continue to report pain almost 1 year after surgery.

Arterial pressure above the upper cerebral autoregulation limit during cardiopulmonary bypass is associated with postoperative delirium

BACKGROUND Mean arterial pressure (MAP) below the lower limit of cerebral autoregulation during cardiopulmonary bypass (CPB) is associated with complications after cardiac surgery. However, simply raising empiric MAP targets during CPB might result in MAP above the upper limit of autoregulation (ULA), causing cerebral hyperperfusion in some patients and predisposing them to cerebral dysfunction after surgery. We hypothesized that MAP above an ULA during CPB is associated with postoperative delirium. METHODS Autoregulation during CPB was monitored continuously in 491 patients with the cerebral oximetry index (COx) in this prospective observational study. COx represents Pearsons correlation coefficient between low-frequency changes in regional cerebral oxygen saturation (measured with near-infrared spectroscopy) and MAP. Delirium was defined throughout the postoperative hospitalization based on clinical detection with prospectively defined methods. RESULTS Delirium was observed in 45 (9.2%) patients. Mechanical ventilation for >48 h [odds ratio (OR), 3.94; 95% confidence interval (CI), 1.72-9.03], preoperative antidepressant use (OR, 3.0; 95% CI, 1.29-6.96), prior stroke (OR, 2.79; 95% CI, 1.12-6.96), congestive heart failure (OR, 2.68; 95% CI, 1.28-5.62), the product of the magnitude and duration of MAP above an ULA (mm Hg h; OR, 1.09; 95% CI, 1.03-1.15), and age (per year of age; OR, 1.01; 95% CI, 1.01-1.07) were independently associated with postoperative delirium. CONCLUSIONS Excursions of MAP above the upper limit of cerebral autoregulation during CPB are associated with risk for delirium. Optimizing MAP during CPB to remain within the cerebral autoregulation range might reduce risk of delirium. CLINICAL TRIAL REGISTRATION clinicaltrials.gov NCT00769691 and NCT00981474.

Efficacy of intravenous patient-controlled analgesia after supratentorial intracranial surgery: a prospective randomized controlled trial. Clinical article.

OBJECT Opioid administration following major intracranial surgery is often limited by a presumed lack of need and a concern that opioids will adversely affect postoperative outcome and interfere with the neurological examination. Nevertheless, evidence is accumulating that these patients suffer moderate to severe postoperative pain and that this pain is often undertreated. The authors hypothesized that intravenous patient-controlled analgesia (PCA) would safely and more effectively treat postoperative supratentorial craniotomy pain than conventional as needed (PRN) therapy. METHODS Following a standardized course of general anesthesia, adult patients who underwent elective supratentorial intracranial surgery were randomized in the neurosciences intensive care unit to receive either PRN intravenous fentanyl 25-50 microg every 30 minutes or PCA intravenous fentanyl 0.5 microg/kg every 15 minutes (maximum 4 doses/hour). The authors measured pain (self-reported scale score [0-10]), sedation (Ramsay Sedation Scale score), Glasgow Coma Scale score, fentanyl use, and major adverse events (excessive sedation, respiratory depression, pruritus, nausea, or vomiting) hourly. RESULTS Sixty-four patients with a mean age of 48 years (range 22-77 years) were randomized to intravenous PCA (29 patients) or PRN fentanyl (35 patients) groups. There were no statistically significant demographic differences between the 2 groups. Patients receiving intravenous PCA had significantly lower pain scores than those receiving intravenous PRN fentanyl (2.53 +/- 1.96 vs 3.62 +/- 2.11 [p = 0.039]) and received significantly more fentanyl than the PRN group (44.1 +/- 34.5 vs 23.6 +/- 23.7 microg/hour [p = 0.007]). There were no differences between the 2 groups regarding the number of patients with adverse events. CONCLUSIONS Intravenous PCA more effectively treats the pain of supratentorial intracranial surgery than PRN fentanyl, and patients in the former group did not experience any untoward events related to the self-administration of opioids.