Anesthesia Literature Review

J. Lance Lichtor, M.D., and Joseph F. Antognini, M.D., Editors 

Although much is known about patient risk factors for infant mortality from surgical repair of congenital diaphragmatic hernia (CDH), the role of hospital factors is not known. In a retrospective analysis of the Pediatric Health Information System database, data from 2203 infants who underwent CDH repair in 37 hospitals between 2000 and 2008 were evaluated. Hospitals were grouped based on average yearly volume of CDH cases. These were low (6 or fewer), medium (6.1–10.0), and high (more than 10.0) volume centers that accounted for 35.1, 40.5, and 24.3% of all hospitals per group, respectively. Infants treated at low-volume CDH hospitals were more likely to be boys, have higher birth weight, and be government insured.

Overall mortality was 18%. Infants treated at low-volume CDH hospitals had significantly higher mortality rate compared with medium- and high-volume hospitals (P = 0.01).

In this large retrospective study of pediatric patients undergoing CDH repair, low-volume CDH hospitals had higher mortality rates than high-volume hospitals. Additional risk factors included lower birth weight, year of admission, presence of chromosomal anomalies, the need for nitrous oxide or extracorporeal membrane oxygenation, age at time of CDH repair, and use of thoracic versus  abdominal approach for repair. This study supports establishing and using regionalized centers of excellence for CDH management in infants.

The Netherlands has a high rate of older mothers, multiple pregnancies, and mothers in ethnic minorities, which may contribute to it having one of the highest perinatal mortality rates (1.1%) in Europe. In addition, the Dutch use a two-tiered system whereby women with a low risk of morbidity receive primary care from independent midwives, whereas those with a higher risk of morbidity receive secondary obstetric-supervised perinatal care. The rate of perinatal death and morbidity among normally formed term infants (N = 37,735) was evaluated using data from a prospective cohort study of women who received care from midwives and obstetricians.

Of 50% of infants born to women who started labor in primary care, 29% were referred to secondary care; 65% of all infants were born under the supervision of an obstetrician. Overall perinatal death rate was 2.62 per 1000 babies delivered, which was significantly higher in nulliparous women compared with multiparous women. Neonates whose mothers started labor in midwife-supervised primary care had a significantly higher risk of delivery-related perinatal death, as did women who were referred from a midwife to an obstetrician when compared with women who started with secondary care.

This data, generated from the Dutch Obstetric System registry, suggests that the risk of delivery-related perinatal death was higher among patients with low-risk pregnancy and midwife-supervised perinatal care versus  those with high-risk pregnancy and obstetric-supervised perinatal care. The authors suggest that the increased risk of perinatal death in the Netherlands may be related to this two-tier obstetric delivery system.

In an attempt to reduce the disproportionate number of in-hospital adverse events associated with surgical care, several surgical checklists, new training programs, and efforts to improve quality communications have been developed. A controlled, multicenter, prospective study assessed the effects of implementation of the SURgical PAtient Safety System (SURPASS) checklist, a multidisciplinary checklist that includes preoperative, perioperative, and postoperative steps.

A total of 4364 surgical procedures was included in the preimplementation cohort; 4,387, in the postimplementation cohort. After implementation, complications significantly decreased (10.6 events per 100 patients). When more of the checklist was completed, the complication rate was also lower. Decreases were also observed for in-hospital mortality (−0.7%), the proportion of patients with temporary disability (−2.7%), and the proportion of patients that required a second procedure to resolve a complication (−1.1%). After controlling for potential confounding factors, the checklist demonstrated an absolute reduction of 9.7 complications per 100 patients.

Typically, the use of checklists is confined to the immediate perioperative period. This study evaluated a comprehensive safety checklist for surgical patients from admission to discharge. Checklist use was associated with decreased in-hospital perioperative mortality and complications.

The risk for acute kidney injury (AKI) may be increased for patients undergoing surgery with same-admission cardiac catheterization for multiple preoperative and postoperative reasons. To assess the effect of timing in cardiac catheterization and cardiac surgery on AKI, a prospective cohort study of patients undergoing catheterization (N = 668) underwent cardiac surgery during the same hospital admission or during a later admission.

The overall incidence of AKI was 45%. AKI was associated with an increased risk of in-hospital mortality, low cardiac output failure, and pneumonia. The incidence of AKI was significantly higher among patients who had same-admission catheterization (50.2 vs.  33.7%; P = 0.001).

The risk of AKI in a group of patients that requires surgical management simultaneous to admission with cardiac catheterization is a component of the overall risk present for AKI among patients who do not leave the hospital before surgery.

AKI is a serious complication after cardiopulmonary bypass. This study showed that patients who underwent cardiac catheterization and later hospitalization for surgery had lower incidence of AKI than patients who underwent cardiac catheterization and surgery during hospitalization. Increased time, when feasible, may reduce AKI, which is associated with increased mortality. However, other factors related to urgent surgery may contribute to AKI risk.

Jean Mantz, M.D., Ph.D., Editor 

The number of elderly patients with subarachnoid hemorrhage is increasing. However, the effects of age on angiographic vasospasm, delayed ischemic neurologic deficits, and abnormal transcranial Doppler measurements are unknown. A retrospective analysis of data from an international multicenter, double-blind, randomized, placebo-controlled study (Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage) of clazosentan was conducted to assess age-dependent differences in the incidence of cerebral vasospasm.

Of 413 patients included in the study, 11% were aged at least 65 yr. Overall, 45% of patients had angiographic vasospasm; 19%, delayed ischemic neurologic deficits; and 81%, abnormal transcranial Doppler measurements. Although there was no significant relationship between age and any vasospasm outcome measure, sex, World Federation of Neurosurgical Societies grade, subarachnoid clot size, aneurysm treatment modality, clazosentan treatment, ventriculostomy, rescue therapy, and phenytoin were significant predictors of angiographic vasospasm.

Vasospasm is a dreaded complication of subarachnoid hemorrhage. The ability to identify factors that increase the incidence of vasospasm could help to guide treatment and improve prognostic accuracy. These data suggest, however, that advancing age is not associated with increased incidence of vasospasm.

Although hundreds of thousands of patients survive severe sepsis annually, these patients may experience long-term complications, such as cognitive and functional impairments. Using national prospective cohort analysis (Health and Retirement Study), the authors assessed potential correlations among severe sepsis and subsequent cognitive impairments among patients older than 50 yr.

Throughout 7 yr (1998–2005), a total of 517 patients survived 623 episodes of severe sepsis and had at least one follow-up survey. Patients were observed for up to 7.8 yr before experiencing sepsis and up to 8.3 yr afterward.

The prevalence of moderate to severe cognitive impairment increased by approximately 10% among sepsis survivors (16.7 vs.  6.1%; P < 0.001). Survivors also were at a greater risk for functional limitations. Severe sepsis contributed to long-term disability when assessed on a per-patient basis and included 1.57 and 1.50 new limitations for patients with no or mild-to-moderate limitations before sepsis, respectively. Furthermore, these patients experienced 0.51 new limitations per year after sepsis. Results were similar among patients regardless of mechanical ventilation and hospitalization requirements before severe sepsis.

Hospitalization and cognitive decline among older patients has been established previously. This cohort study demonstrates the impact of sepsis in accelerating cognitive decline and disability among older patient populations after sepsis survival. A remarkable feature of this study is that baseline cognitive status was available for all subjects. There is now a large body of recent work that supports the concept of central nervous system deterioration of multiple etiologies, including sepsis, among older patients hospitalized for critical illness.

Delirium among patients in the intensive care unit (ICU) is associated with prolonged ventilation, hospital-acquired pneumonia, and increased hospital length of stay, as well as mortality. To further assess the association between the length of delirium and clinical outcomes, a prospective cohort analysis was conducted as part of a multicenter, randomized, controlled trial comparing dexmedetomidine and midazolam (Safety and Efficacy of Dexmedetomidine Compared to Midazolam).

From the total study population, 354 patients met the a priori –defined inclusion criteria for this cohort study (i.e ., at least one delirium assessment). Overall prevalence of delirium was 64.4%. Among patients with delirium, 30-day all-cause mortality was significantly higher when compared with patients without delirium (30.3 vs.  11.9%; P < 0.001). Median time to extubation (10.7 vs.  3.6 days) and median ICU length of stay (16 vs.  4 days) were also significantly higher among patients with delirium (P < 0.001). Delirium duration was a significant independent predictor of 30-day mortality (P < 0.001), as were age (P = 0.01) and Acute Physiology and Chronic Health Evaluation II score (P = 0.02). Likewise, delirium duration was associated with time on mechanical ventilation (P < 0.001) and ICU length of stay (P < 0.001).

This subgroup analysis of delirious patients enrolled in the Safety and Efficacy of Dexmedetomidine Compared to Midazolam trial indicates that, after adjusting for covariates, delirium duration was the strongest predictor of ventilation time, ICU stay, and death. However, because of the high incidence of delirium observed in this study (as diagnosed by the Confusion Assessment Method in the ICU in comparison with other clinical scales), it would be interesting to identify the role of level of consciousness in these results.

Delirium is frequent after cardiac surgery and is associated with an increased rate of postoperative complications and death. However, because of the multifactoral nature in the pathophysiology of postoperative delirium, advanced methodology for differentiating delirious and nondelirious patients is needed. Based on previous studies, the authors hypothesized that bilateral four-channel bispectral electroencephalography (BIS-EEG) would be able to detect differences in delirium of patients after cardiac surgery in which consciousness, arousal, and delirium were also assessed using the Confusion Assessment Method for the intensive care unit (ICU).

ICU delirium, as determined on postoperative day 1, identified 32 delirious and 82 nondelirious patients. Patients with delirium were significantly older than those without delirium (73.3 vs.  67.3 yr; P = 0.015). Because of technical difficulties, BIS-EEG was analyzed in 102 patients. Of those 102 patients, BIS-EEG and spectral edge frequency (SEF) were significantly lower among delirious versus  nondelirious patients. Components of BIS-EEG, electromyography (EMG), and signal quality index (SQI) were similar between groups. BIS-EEG data were positively correlated with Richmond Agitation-Sedation Scale scores and BIS EMG and negatively correlated with serum cortisol concentration. Bilateral BIS, as a predictor of intensive care unit delirium, had 27% sensitivity and 96% specificity with overall accuracy of 76%.

This study suggests that bilateral BIS-EEG may exhibit high specificity, albeit low sensitivity, in predicting postoperative delirium in this clinical setting. The interest in inflammatory biomarkers for predicting or monitoring postoperative delirium needs further investigation.

Timothy J. Brennan, Ph.D., M.D., Editor 

Although numerous studies have demonstrated a high incidence of long-term pain after thoracotomy, the incidence of neuropathic pain has not been clearly defined because of the absence of standardized evaluation and diagnostic criteria. To determine the incidence of neuropathic pain after thoracotomy, this prospective study used validated screening tools for neuropathic pain, as recently announced by the Neuropathic Pain Special Interest Group Task Force of the International Association for the Study of Pain.

Patients (N = 49) with postsurgical thoracic pain after lateral or posterolateral thoracotomy for focal bronchopulmonary carcinoma were included. Persistent pain was reported in 70% of 38 patients at 6 months. Pain was generally localized with T5-T6 dermatomes at the operated side. The incidence of neuropathic pain among all patients undergoing surgery was at least 29%. Of all patients with pain at 6 months, 49% were probable neuropathic pain.

Many patients complain of persistent pain after thoracotomy. Intercostal nerve damage is thought to make a major contribution to clinical symptoms. Although postthoracotomy pain syndrome is common, neuropathic pain as an etiology represents a minority of patients with postthoracotomy pain syndrome. Other pain generators must be considered. The article's accompanying editorial notes the difficulty in trying to match signs, symptoms, and etiology of persistent pain.

Approximately 4 million Americans, including 3% of all U.S. adults with noncancer pain, are receiving long-acting or extended-release opioids annually from more than 1 million Drug Enforcement Administration–registered prescribers. There has been increasing concern regarding drug abuse and overdose deaths with these medications. Recently an advisory panel from the U.S. Food and Drug Administration announced that the proposed Risk Evaluation and Mitigation Strategy for these compounds was not sufficient.

Unintentional drug overdoses are the second leading cause of accidental death. In 2007, unintentional drug overdoses accounted for more deaths than heroin and cocaine combined. Based on substance-abuse treatment program admission records, prescription painkillers are the second most commonly abused drug. Death rates are higher among men and usually occur in individuals aged 45–54 yr.

Developing an appropriate Risk Evaluation and Mitigation Strategy program has been difficult. There is disagreement on whether such a program should include all opioids, or simply long-acting opioids. Furthermore, there are concerns regarding the burden to the healthcare system: (1) who pays for physician training (e  .  g  . , pharmaceutical companies, government), (2) who enforces mandatory training (e.g. , state medical licensing boards, federal legislation). Others have expressed concern that, if guidelines are too stringent, necessary patient treatments may be limited or prohibited entirely.

It is anticipated that the final plan will be announced this year and that manufacturers will have up to 120 days to comply.

In the past 20 yr, the use of opioids to manage chronic pain has increased. In parallel with increased use is an increased rate of death from unintentional opioid overdose. As a result, the U.S. Food and Drug Administration is considering guidelines and training for physicians who prescribe these drugs.

Conditions such as complex regional pain syndrome and arthritis have been associated with peripheral elevations in endocannabinoid concentrations. This finding suggests a potential role of endocannabinoids in neuropathic and inflammatory pain modulation. However, similar to endogenous opioids, endocannabinoids have a relatively short half-life. Therefore, inhibitors of the anandamide-degrading enzyme fatty acid amide hydrolase were developed.

Despite being a lipophilic molecule, URB937 suppressed fatty acid amide hydrolase activity in peripheral tissues, but not in the brain, of mice and rats. In mice, intraperitoneal injection (1 mg/kg) of URB937 increased anandamide and other fatty acid amide hydrolase substrates in peripheral tissues, but not in the brain. Subcutaneous injection of URB937 produced antinociception as demonstrated by acetic acid–induced writhing, hyperalgesia caused by peripheral nerve injury, and formalin-induced pain.

Cannabinoids represent a potential new analgesic tool for perioperative medicine. Currently available cannabinoid agonists do not have strong clinical analgesic efficacies. This study suggests that inhibiting cannabinoid degradation may be a novel approach for enhancing the analgesic effects of endogenous cannabinoids and exogenous cannabinoid agonists.