Stress cardiovascular MR in routine clinical practice: referral patterns, accuracy, tolerance, safety and incidental findings.

OBJECTIVE: The use of stress cardiovascular MR (CMR) to evaluate myocardial ischaemia has increased significantly over recent years. We aimed to assess the indications, incidental findings, tolerance, safety and accuracy of stress CMR in routine clinical practice. METHODS: We retrospectively examined all stress CMR studies performed at our tertiary referral centre over a 20-month period. Patients were scanned at 1.5 T, using a standardised protocol with routine imaging for late gadolinium enhancement. Angiograms of patients were assessed by an interventional cardiologist blinded to the CMR data. RESULTS: 654 patients were scanned (mean age 65±29 years; 63 inpatients; 9.6%). 14% of patients had incidental extracardiac findings, the commonest being liver or renal cysts (6%) and pulmonary nodules (4%). 639 patients (97.7%) received intravenous adenosine, 10 received intravenous dobutamine and 5 patients had both. Of the 15 patients who received dobutamine, 12 had no side-effects/complications, 2 experienced nausea and 1 chest tightness. Of the 644 patients who received adenosine, 43% experienced minor symptoms, 1% had transient heart block and 0.2% had severe bronchospasm requiring termination of infusion. There were no cases of hospitalisation or myocardial infarction. 241 patients also had coronary angiography. For detecting at least moderate stenosis of ≥50%, sensitivity was 86%, specificity 98% and accuracy 89%. For detecting severe stenoses of ≥70%, sensitivity was 91%, specificity 86% and overall accuracy 90%. These results compare very favourably with previous smaller research studies and meta-analyses. CONCLUSION: We conclude that stress CMR, with adenosine as the main stress agent, is well tolerated, safe and accurate in routine clinical practice.

Improving immunization coverage through budgeted microplans and sub-national performance agreements: early experience from Cambodia.

In recent years, Cambodia has demonstrated significant success in specific aspects of immunization with gains through campaign efforts in measles control and polio eradication. In contrast, routine immunization rates have failed to improve over the last five years. In response, the National Immunization Program of the Ministry of Health developed a coverage improvement planning (CIP) process. This paper describes the CIP process in Cambodia, including identified barriers to and strategies for improving coverage. Immunization coverage rose in 8 of 10 pilot districts in the year following the introduction of CIP in 2003. The mean increase in DPT3 coverage across pilot districts on an annual basis was 16%, which provides encouraging early evidence for the effectiveness of the intervention. Factors associated with success in coverage improvement included: (1) development of a needs-based micro-plan, (2) application of performance-based contracting between levels of management, (3) investment in social mobilization, (4) securing finance for health outreach programs and (5) strengthened monitoring systems. Lessons learned will guide program expansion to improve immunization coverage nationally.

Pharmacokinetics and pharmacodynamics of enantiomers of ibuprofen and flurbiprofen after oral administration.

The main objective of this study was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model for the analgesic effect of ibuprofen and flurbiprofen using subjective as well as objective parameters. Serum concentrations of the individual enantiomers after oral administration of racemic ibuprofen (400 mg) and flurbiprofen (100 mg) were monitored using reversed phase HPLC. The pharmacokinetic data of the S-enantiomer was linked to the effect data using a hypothetical effect compartment. The effect data were fitted to Emax model. PK/PD analysis were performed using both objective (evoked potentials) and subjective (pain intensity scale) parameters. Concentrations of S-ibuprofen were found to be consistently larger than of R-ibuprofen and differed in various pharmacokinetic parameters after oral administration of racemic ibuprofen. Pharmacokinetic parameters of the enantiomers of flurbiprofen, such as volume of administration and clearance, also differed. Comparison of cumulative effects calculated as the area under the effect-time curve (AUCE) showed a statistically significant difference from placebo for both ibuprofen and flurbiprofen using evoked potential values. However, using pain rating values ibuprofen AUCE did not differ statistically significant from placebo whereas flurbiprofen AUCE did. PK/PD modeling of both evoked potentials and pain rating data than in evoked potential data. Hence, EP monitoring may allow to evaluate analgesic activity with a smaller number of subjects than pain rating.

Pharmacodynamic evaluation of codeine using tooth pulp evoked potentials.

Pain assessment in human volunteers is difficult, and it often requires a large number of subjects to show analgesic efficacy with statistical significance. Electrical tooth pulp stimulation elicits a painful sensation and produces an electroencephalographic (EEG) signal that can be recorded from the scalp when precisely controlled dental stimuli are delivered. These somatosensory evoked potentials (EP) consist of a series of peaks or waves each characterized by their polarity, latency, and amplitude. They are obtained by processing the EEG signals that occur after tooth pulp stimulation. There is good correlation between subjective pain reports and evoked potential amplitudes (N150-P250 component). Thus, EP may provide a useful model for the assessment of analgesic activity in human volunteers. We describe an improved method for producing and recording tooth pulp evoked potentials in six healthy subjects. Only 16 EEG epochs were necessary to get a reproducible EP response from the participants. The approach was applied to study the efficacy of codeine (60 mg administered orally); a decrease in the evoked potential amplitudes after codeine administration was observed. The data were consistent with results from visual analog pain ratings given by the subjects.

Metabolism of dynorphin A1-13 in human CSF.

In-vitro incubation of human cerebrospinal fluid (CSF) obtained from patients ranging from 22-78 years with 10 microM of dynorphin A1-13 (Dyn A1-13) resulted in several cleavage products. Dyn A1-12 and A2-13 were identified as the major CSF metabolites by matrix-assisted laser desorption mass spectrometry (LD-MS). Further metabolites were Dyn A1-6, A2-12 and A4-12. LD-MS further suggested the formation of Dyn A1-8, A1-7, A1-10, A7-10, A3-12, A7-12, A3-13, A7-13 and A8-13. The metabolic half-life of Dyn A1-13 at 37 degrees C was approximately 2.5 h (range 1.75-8.5 h), compared to less than one minute in plasma. The half-life of Dyn A1-13 decreased markedly with age or age-associated processes (n = 20, r2 = 0.498). Noncompartmental kinetic analysis in the absence or presence of enzyme inhibitors (leucinethiol 10 microM, captopril 100 microM and GEMSA 20 microM) suggested that Dyn A1-13 is mainly metabolized by carboxypeptidase to A1-12 (51%) and by aminopeptidases to A2-13 (35%). The generation of A1-6 (13%) was only detected under enzyme inhibition. The extent of conversion into the main metabolites did not follow an age-associated trend, thus over-all enzyme levels but no specific enzymatic systems are elevated with age.

Three balanced anesthetic techniques for neuroanesthesia: infusion of thiopental sodium with sufentanil or fentanyl compared with inhalation of isoflurane.

STUDY OBJECTIVE: To compare emergence from anesthesia and the hemodynamic and respiratory depressant effects of thiopental sodium infusion plus sufentanil or fentanyl with those of isoflurane as the primary component of a balanced technique for neuroanesthesia. DESIGN: Randomized, double-blind, prospective study. SETTING: University hospital and its affiliated Veterans Affairs Medical Center. PATIENTS: Thirty patients undergoing elective craniotomy for aneurysm or tumor. INTERVENTIONS: Thiopental with infusion of sufentanil 0.1 microgram/kg/hr, thiopental with infusion of fentanyl 1 microgram/kg/hr, or inhalation of 0.25% to 2% isoflurane as the major component of a balanced anesthesia technique that included nitrous oxide (N2O) and vecuronium (potency ratio of sufentanil to fentanyl, 10:1). MEASUREMENTS AND MAIN RESULTS: Intraoperative stress response (as indicated by intraoperative hypertension) was said to be the percentage of time the patient required administration of an antihypertensive drug, measuring from the first dose of thiopental to discontinuation of N2O at the end of the procedure, excluding any period of induced hypotension. Rapidity of emergence was measured by the number of minutes from discontinuation of N2O to first opening of the eyes on command. Adequacy of spontaneous ventilation was evaluated by determining partial pressure of arterial carbon dioxide 1, 2, and 3 hours after discontinuation of N2O. Extent of vasoactive drug administration for control of intraoperative hypertension (as determined by the clinicians caring for the patients) was described by minutes of vasodilator infusion and milligrams of propranolol or labetalol administered. The frequency of postoperative hypertension was defined as the number of patients in each group who required medication for postoperative hypertension. No significant differences in variables were found for thiopental/sufentanil, thiopental/fentanyl, or isoflurane when these drugs were used with N2O and vecuronium. CONCLUSIONS: Any one of these balanced anesthetic techniques appears appropriate for craniotomy.

Characteristics of nurse anesthetists working with and without anesthesiologists.

All professionally active certified registered nurse anesthetists (CRNAs) in four geographically representative states were surveyed by mail and telephone in 1981, and response rate of greater than or equal to 70% was obtained for each state. CRNAs who worked with anesthesiologists (Group I) were compared with those who worked in hospitals with no anesthesiologists (Group II). More than 75% of both groups were employed by hospitals, but Group II CRNAs (15.5% of respondents) were nearly five times as likely to practice on an independent, fee-for-service basis. Members of Group II worked predominantly in hospitals in small or rural communities and, compared with those in Group I, were more likely to be male and older, less likely to hold a baccalaureate degree, and less likely to use invasive monitoring techniques. Nearly 50% of Group II had no standing consulting relationship with an anesthesiologist. A consultation network supported by telecommunications deserves consideration as a means of providing CRNAs who work independently in small rural hospitals with a cost-effective team approach to anesthesia care.

Electrophysiological evaluation of the patient with acute spinal cord injury.

This article reviews basic principles, equipment and techniques, and clinical applications of electrophysiologic monitoring in patients with spinal cord injuries. Four groups of electrophysiologic measurements are considered: Somatosensory evoked potentials (SEPs); motor evoked potentials (MEPs); electromyography (EMG) and nerve conduction studies; and late responses, including H reflex, M response, and F wave. Reports of SEP recordings in spinal cord injury, as drawn from the literature, are tabulated in detail.

Monitoring of sensory evoked potentials is highly reliable and helpful in the operating room.

Because short-latency evoked potentials are relatively resistant to anesthetic agents, they can be used to monitor neural pathways during surgical procedures. The use of median nerve somatosensory evoked potentials to localize the central sulcus is an established aid of indisputable value in neurosurgical procedures involving cortical incisions for resection of certain epileptic foci, vascular malformations, or neoplasms near the central area of the brain. Likewise, recording of intraoperative nerve action potentials is currently regarded as indispensable in management of the neuroma-incontinuity after peripheral nerve trauma, as this evoked potential monitoring technique provides the only reliable method of distinguishing between axonotmetic and neurotmetic lesions. Evoked potential monitoring has been of value during many other types of surgical procedures, including cerebral aneurysm clipping, carotid endarterectomy, aortic procedures, microvascular decompression for trigeminal neuralgia and hemifacial spasm, acoustic neuroma resection, and a variety of spinal procedures. A detailed review of the literature is presented on the use of evoked potential monitoring for one of the more common indications: scoliosis surgery. Many orthopedic surgeons use the "wake-up test" only if the somatosensory evoked potentials change during surgery. A detailed review of the few reported cases of "false negative" evoked potentials is presented. The dearth of convincing reports of such phenomena in the face of so many positive experiences should persuade even the skeptical that monitoring of evoked potentials is a highly reliable and helpful intraoperative tool.

EEG changes during carotid endarterectomy: drug effect and embolism.

Clinical neurological status and the electroencephalogram (EEG) were monitored during right carotid endarterectomy under regional anaesthesia in a patient who had suffered two prior cerebral infarctions. No change in EEG or clinical status was seen with occlusion of the carotid artery, but generalized encephalopathic changes were seen after a small dose of narcotic given before carotid occlusion. Bihemispheric changes in EEG and neurological status occurred upon release of carotid occlusion. This case demonstrates three important points. First, EEG changes can be seen with sedative or anaesthetic agents in patients who have previously suffered brain injury. Second, temporary neural dysfunction may be seen remote from the site of a localized injury to the brain--a phenomenon known as diaschisis. Finally, this report reiterates the observation that the risk of injury to the brain during carotid endarterectomy is not limited to the period of possible ischaemia during occlusion of the carotid artery.

Challenge with rubella virus after loss of detectable vaccine-induced antibody.

Studies were conducted of experimental challenge with rubella virus in vaccinees whose possession of vaccine-induced antibody after vaccination had been documented and whose antibody level had become undetectable or very low over time. The challenge virus was the Howell strain, which had been shown to produce typical clinical and laboratory features of rubella in susceptible persons. The challenge of the vaccinees resulted in local viral replication in all but one; in viremia, a primary immunologic response, and a secondary antibody response in some; and usually in illness without a rash or in subclinical infection. The results emphasize the importance of continuing careful clinical and laboratory surveillance of vaccinees for determining the persistence of vaccine-induced immunity and of considering methods for identifying and revaccinating the minority of vaccinees who lose such immunity.

Intraoperative monitoring of brain-stem auditory evoked potentials.

Brain-stem auditory evoked potentials (BAEP) were monitored during 545 neurosurgical operations in the cerebellopontine angle. The BAEP were irreversibly obliterated in five patients who required deliberate section of the auditory nerve. Technical difficulties interfered with monitoring in three cases, and three patients had deafness and absent BAEP preoperatively. Reversible alterations in BAEP were seen during 32 operations, with recovery after as long as 177 minutes of virtually complete obliteration. Changes in BAEP were associated with surgical retraction, operative manipulation, positioning of the head and neck for retromastoid craniectomy, and the combination of hypocarbia and moderate hypotension. In 19 cases, waveforms improved after specific interventions made by the surgeon or anesthesiologist because of deteriorating BAEP. In 13 other cases, BAEP recovered after maneuvers not specifically related to the electrophysiological monitoring, most often completion of operative manipulation. Whenever BAEP returned toward normal by the end of anesthesia, even after transient obliteration, hearing was preserved. Irreversible loss of BAEP occurred only when the auditory nerve was deliberately sacrificed. The authors conclude that monitoring of BAEP may help prevent injury to the auditory nerve and brain stem during operations in the cerebellopontine angle.

Causes of stroke in carotid endarterectomy.

Carotid endarterectomy performed with the patient conscious under regional anesthesia provides a unique opportunity to determine the time of onset of a neurologic deficit and in deduce a likely cause. If a trial period of carotid occlusion is tolerated without the development of a neurologic deficit (96% of our patients), operation may continue without indwelling shunt. Of the 345 patients who had elective carotid endarterectomies performed without shunt, neurologic deficits lasting longer than 24 hours developed in 6 patients (1.7%), and deficits resolving within 24 hours occurred in 15 patients (4.3%). The neurologic deficit developed during carotid dissection in 3 patients, during carotid occlusion in 1 patient, upon release of carotid occlusion in 2 patients, and in the first 5 postoperative days in 15 patients. Of the 15 postoperative deficits, 9 were transient ischemic attacks similar to preoperative episodes, 4 were strokes, and 2 were visual changes. Twenty of 21 deficits were thromboembolic, reperfusion phenomena or were related to hypotension. Only one (0.3% of 345 cases) could be attributed to cerebral anoxia. We believe comparison of raw stroke rates is not valid in comparing methods of cerebral protection, since most perioperative neurologic deficits are not attributable to hypoperfusion. Furthermore, trial carotid occlusion in the conscious patient is a satisfactory method for determining the need to use a shunt.