Mark T. Keegan

Plasma exchange for severe attacks of CNS demyelination: Predictors of response

The authors reviewed 59 consecutive patients treated with plasma exchange (PE) for acute, severe attacks of CNS demyelination at Mayo Clinic from January 1984 through June 2000. Most patients had relapsing-remitting MS (n = 22, 37.3%), neuromyelitis optica (NMO) (n = 10, 16.9%), and acute disseminated encephalomyelitis (n = 10, 16.9%). PE was followed by moderate or marked functional improvement in 44.1% of treated patients. Male sex (p = 0.021), preserved reflexes (p = 0.019), and early initiation of treatment (p = 0.009) were associated with moderate or marked improvement. Successfully treated patients improved rapidly following PE, and improvement was sustained.

Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange

Early, active multiple sclerosis lesions show four immunopathological patterns of demyelination. Although these patterns differ between patients, multiple active lesions from a given patient have an identical pattern, which suggests pathogenic heterogeneity. Therapeutic plasma exchange (TPE) has been successfully used to treat fulminant demyelinating attacks unresponsive to steroids. We postulated that patients with pattern II would be more likely to improve after TPE than those with other patterns since pattern II lesions are distinguished by prominent immunoglobulin deposition and complement activation. We retrospectively studied 19 patients treated with TPE for an attack of fulminant CNS inflammatory demyelinating disease. All patients with pattern II (n=10), but none with pattern I (n=3) or pattern III (n=6), achieved moderate to substantial functional neurological improvement after TPE (p<0.0001). Patients with multiple sclerosis with pattern II pathology are more likely to respond favourably to TPE than are patients with patterns I or III.

Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody

Objectives: To describe the clinical features and coexisting serum autoantibodies in seven patients with encephalitis associated with autoantibodies to α-dendrotoxin-sensitive voltage-gated potassium channels (VGKCs), and to compare this disorder with other autoimmune encephalopathies. Methods: Clinical information was obtained from a retrospective review of medical records and telephone interviews. All autoantibody testing was performed in a single laboratory. Results: The seven patients were examined for subacute cognitive and behavioral changes. Seizures, usually temporal-onset complex partial type, were documented in six patients, and all seven patients had EEG abnormalities. None had symptoms or signs of neuromuscular hyperexcitability. One described hypersalivation. Four patients had additional autoantibody markers of neurologic autoimmunity (muscle acetylcholine receptor, striational, P/Q-type calcium channel, or GAD65), and two had thyroperoxidase antibodies. Two patients had a history of cancer: one had active prostate adenocarcinoma, and the second had a remote history of tongue carcinoma. Cranial MRI demonstrated mesial temporal lobe abnormalities in all patients. One patient improved spontaneously, and six were treated with IV methylprednisolone. Three improved remarkably with treatment. At follow-up evaluation, one had no cognitive deficits, four had mild persistent short-term memory dysfunction, and two had persistent disabling behavioral deficits. Conclusions: Voltage-gated potassium channel antibodies are a valuable serologic marker of a potentially reversible autoimmune encephalopathy. The neurologic manifestations of this disorder are indistinguishable from paraneoplastic limbic encephalitis but are distinct from Morvan syndrome and Hashimoto encephalopathy.

Intraoperative Tidal Volume as a Risk Factor for Respiratory Failure after Pneumonectomy

Background:Respiratory failure is a leading cause of postoperative morbidity and mortality in patients undergoing pneumonectomy. The authors hypothesized that intraoperative mechanical ventilation with large tidal volumes (VTs) would be associated with increased risk of postpneumonectomy respiratory failure. Methods:Patients undergoing elective pneumonectomy at the authors’ institution from January 1999 to January 2003 were studied. The authors collected data on demographics, relevant comorbidities, neoadjuvant therapy, pulmonary function tests, site and type of operation, duration of surgery, intraoperative ventilator settings, and intraoperative fluid administration. The primary outcome measure was postoperative respiratory failure, defined as the need for continuation of mechanical ventilation for greater than 48 h postoperatively or the need for reinstitution of mechanical ventilation after extubation. Results:Of 170 pneumonectomy patients who met inclusion criteria, 30 (18%) developed postoperative respiratory failure. Causes of postoperative respiratory failure were acute lung injury in 50% (n = 15), cardiogenic pulmonary edema in 17% (n = 5), pneumonia in 23% (n = 7), bronchopleural fistula in 7% (n = 2), and pulmonary thromboembolism in 3% (n = 1). Patients who developed respiratory failure were ventilated with larger intraoperative VT than those who did not (median, 8.3 vs. 6.7 ml/kg predicted body weight; P < 0.001). In a multivariate regression analysis, larger intraoperative VT (odds ratio, 1.56 for each ml/kg increase; 95% confidence interval, 1.12–2.23) was associated with development of postoperative respiratory failure. The interaction between larger VT and fluid administration was also statistically significant (odds ratio, 1.36; 95% confidence interval, 1.05–1.97). Conclusion:Mechanical ventilation with large intraoperative VT is associated with increased risk of postpneumonectomy respiratory failure.

Toward the prevention of acute lung injury: Protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion

Objective:We evaluated the effect of two quality improvement interventions (low tidal volume ventilation and restrictive transfusion) on the development of acute lung injury in mechanically ventilated patients. Design:Observational cohort study. Setting:Three intensive care units in a tertiary academic center. Patients:We included patients who were mechanically ventilated for ≥48 hrs excluding those who refused research authorization or had preexisting acute lung injury or pneumonectomy. Interventions:Multifaceted interdisciplinary intervention consisting of Web-based teaching, respiratory therapy protocol, and decision support within computerized order entry. Measurements and Main Results:Of 375 patients who met the inclusion and exclusion criteria, 212 were ventilated before and 163 after the interventions. Baseline characteristics were similar between the two groups except for a lower frequency of sepsis (27% vs. 17%, p = .030), trend toward lower median glucose level (140 mg/dL, interquartile range 118–168 vs. 132 mg/dL, interquartile range 113–156, p = .096), and lower frequency of pneumonia (27% vs. 20%, p = .130) during the second period. We observed a large decrease in tidal volume (10.6–7.7 mL/kg predicted body weight, p < .001), in peak airway pressure (31–25 cm H2O, p < .001), and in the percentage of transfused patients (63% to 38%, p < .001) after the intervention. The frequency of acute lung injury decreased from 28% to 10% (p < .001). The duration of mechanical ventilation decreased from a median of 5 (interquartile range 4–9) to 4 (interquartile range 4–8) days (p = .030). When adjusted for baseline characteristics in a multivariate logistic regression analysis, protocol intervention was associated with a reduction in the frequency of new acute lung injury (odds ratio 0.21, 95% confidence interval 0.10–0.40). Conclusions:Interdisciplinary intervention effectively decreased large tidal volumes and unnecessary transfusion in mechanically ventilated patients and was associated with a decreased frequency of new acute lung injury.

Severity of illness scoring systems in the intensive care unit

Objective:Adult intensive care unit prognostic models have been used for predicting patient outcome for three decades. The goal of this review is to describe the different versions of the main adult intensive care unit prognostic models and discuss their potential roles. Data Source:PubMed search and review of the relevant medical literature. Summary:The main prognostic models for assessing the overall severity of illness in critically ill adults are Acute Physiology and Chronic Health Evaluation, Simplified Acute Physiology Score, and Mortality Probability Model. Simplified Acute Physiology Score and Mortality Probability Model have been updated to their third versions and Acute Physiology and Chronic Health Evaluation to its fourth version. The development of prognostic models is usually followed by internal and external validation and performance assessment. Performance is assessed by area under the receiver operating characteristic curve for discrimination and Hosmer-Lemeshow statistic for calibration. The areas under the receiver operating characteristic curve of Simplified Acute Physiology Score 3, Acute Physiology and Chronic Health Evaluation IV, and Mortality Probability Model0 III were 0.85, 0.88, and 0.82, respectively, and all these three fourth-generation models had good calibration. The models have been extensively used for case-mix adjustment in clinical research and epidemiology, but their role in benchmarking, performance improvement, resource use, and clinical decision support has been less well studied. Conclusions:The fourth-generation Acute Physiology and Chronic Health Evaluation, Simplified Acute Physiology Score 3, Acute Physiology and Chronic Health Evaluation IV, and Mortality Probability Model0 III adult prognostic models, perform well in predicting mortality. Future studies are needed to determine their roles for benchmarking, performance improvement, resource use, and clinical decision support.

Evidence-based red cell transfusion in the critically ill: Quality improvement using computerized physician order entry

Objective:The implementation of evidence-based practice poses a significant challenge in the intensive care unit. In this quality improvement intervention we assessed the effect of an institutional protocol and computerized decision support for red cell transfusion in the critically ill. Design:We compared processes of care and outcomes during the two 3-month periods before and after the introduction of a multidisciplinary quality improvement intervention. Setting:Multidisciplinary intensive care units—medical, surgical, and mixed—in a tertiary academic center. Patients:Consecutive critically ill patients with anemia (hemoglobin of <10 g/dL). Intervention:Using the computerized provider order entry, we developed an evidence-based decision algorithm for red cell transfusion in adult intensive care units. Measurements and Main Results:We collected information on demographics, diagnosis, severity of illness, transfusion complications, and laboratory values. The main outcome measures were number of transfusions, proportion of patients who were transfused outside evidence-based indications, transfusion complications, and adjusted hospital mortality. The mean number of red cell transfusions per intensive care unit admission decreased from 1.08 ± 2.3 units before to 0.86 ± 2.3 units after the protocol (p<.001). We observed a marked decrease in the percentage of patients receiving inappropriate transfusions (17.7% vs. 4.5%, p< .001). The rate of transfusion complications was also lower in the period after the protocol (6.1% vs. 2.7%, p = .015). In the multivariate analysis, protocol introduction was associated with decreased likelihood of red cell transfusion (odds ratio, 0.43; 95% confidence interval, 0.30 to 0.62). Adjusted hospital mortality did not differ before and after protocol implementation (odds ratio, 1.12; 95% confidence interval, 0.69 to 1.8). Conclusions:The implementation of an institutional protocol and decision support through a computerized provider order entry effectively decreased inappropriate red cell transfusions.

Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration

Abstract Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2–15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p≤0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p≤0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.

The association between nighttime transfer from the intensive care unit and patient outcome.

Objective:To determine the impact of nighttime transfer of patients from the intensive care unit (ICU) on clinical outcome. Design:Retrospective, observational. Setting:Three intensive care units of a tertiary care medical center. Patients:We used prospectively collected information from the Acute Physiology and Chronic Health Evaluation III database of 11,659 patients transferred from the ICU to the regular ward. Interventions:None. Measurements and Main Results:Based on the time of transfer, patients who were transferred from the ICU to the regular ward were categorized into daytime (7:00 am–6:59 pm) and nighttime (7:00 pm–6:59 am) transfers. Patients who were transferred to other ICUs or other facilities, died in the ICU, were discharged home, or did not authorize their medical records to be reviewed for research were excluded. Only the first ICU admission of each patient was considered for outcome analysis. Of the 11,659 study patients, 418 (3.6%) were transferred at night. The first ICU day predicted mortality rate and the last ICU day Acute Physiology Score and Acute Physiology and Chronic Health Evaluation III scores in the nighttime transfer group were higher compared with the daytime transfers. The hospital mortality rate of the nighttime transfers was 5.3% compared with 4.5% of the daytime transfers (p = 0.478). There was no statistically significant difference between the two groups in severity adjusted hospital mortality rate. The ICU readmission rate of the nighttime transfers was higher (12.2% compared with 9.0%, p = 0.027) and the median (interquartile range) hospital length of stay longer (8 [5–15] vs. 7 [4–13] days, p = 0.013) compared with the daytime transfer group. Conclusions:Our study did not find an association between nighttime ICU discharge and hospital mortality. However, the ICU readmission rate was higher and the hospital length of stay longer in the nighttime transfer group.

Management of the difficult and failed airway in obstetric anesthesia

Difficulty with airway management in obstetric patients occurs infrequently and failure to secure an airway is rare. A failed airway may result in severe physical and emotional morbidity and possibly death to the mother and baby. Additionally, the family, along with the medical and nursing staff, may face emotional and financial trauma. With the increase in the number of cesarean sections performed under regional anesthesia, the experience and training in performing endotracheal intubations in obstetric anesthesia has decreased. This article reviews the management of the difficult and failed airway in obstetric anesthesia. Underpinning this important topic is the difference between the nonpregnant and pregnant state. Obstetric anatomy and physiology, endotracheal intubation in the obstetric patient, and modifications to the difficult airway algorithms required for obstetric patients will be discussed. We emphasize that decisions regarding airway management must consider the urgency of delivery of the baby. Finally, the need for specific equipment in the obstetric difficult and failed airway is discussed. Worldwide maternal mortality reflects the health of a nation. However, one could also claim that, particularly in Western countries, maternal mortality may reflect the health of the specialty of anesthesia.