Pacemaker troubleshooting: improved efficacy using a new diagnostic digital Holter recording system.

Asymptomatic dysfunction of cardiac pacing systems is not uncommonly detected using long-term ambulatory monitoring techniques. We report two patients with atrial and ventricular sensing abnormalities noted only on Holter monitoring. Multiple empirical attempts at pacemaker reprogramming based on deductive analysis of the pacing anomaly were unsuccessful. Through the use of a new digital recording system that allowed collection of surface electrocardiographic data, intracardiac electrograms, and Marker Channel data a correct diagnosis was made (pacing lead insulation failure). This new recording system has the advantage of significantly improving diagnostic sensitivity and resulting in cost savings.

What do we really know about antibiotic pharmacodynamics?

Antibiotic pharmacodynamics is an evolving science that focuses on the relationship between drug concentration and pharmacologic effect, which is an antibiotic-induced bacterial death that also can manifest as an adverse drug reaction. The pharmacologic action of antibiotics usually can be described as concentration dependent or independent, although such classifications are highly reliant on the specific antibiotic and bacterial pathogen being studied. Quantitative pharmacodynamic parameters, such as ratio of the area under the concentration-time curve during a 24-hour dosing period to minimum inhibitory concentration (AUC0-24:MIC), ratio of maximum serum antibiotic concentration to MIC (Cmax:MIC), and duration of time that antibiotic concentrations exceed MIC (T>MIC), have been proposed as likely predictors of clinical and microbiologic success or failure for different pairings of antibiotic and bacteria. Thus far, most pharmacodynamic data reported have focused on fluoroquinolones, but work has been conducted on vancomycin, beta-lactams, macrolides, aminoglycosides, and other antibiotics. Despite the development of a number of different pharmacodynamic modeling systems, remarkable agreement exists between in vitro, animal, and limited human data. Although still somewhat premature and requiring additional clinical validation, antibiotic pharmacodynamics will likely advance on four fronts: the science should prove to be extremely useful and represent a cost-effective and efficient method to help develop new antibiotics; formulary committees will likely use pharmacodynamic parameters to assist in differentiating antibiotics of the same chemical class in making antibiotic formulary selections; pharmacodynamic principles will likely be used to design optimal antibiotic strategies for patients with severe infections; and limited data to date suggest that the application of pharmacodynamic concepts may limit or prevent the development of antibiotic resistance. The study of antibiotic pharmacodynamics appears to hold great promise and will likely become a routine part of our daily clinical practices.

Comparison of the adaptive functioning of children prenatally exposed to alcohol to a nonexposed clinical sample.

BACKGROUND: Several studies show impairments in the social and adaptive behaviors of children prenatally exposed to alcohol. However, there remains limited consensus on whether the alcohol exposure directly affects social functioning or whether its effect is mediated by deficits in IQ. In addition, no studies have investigated whether deficits in social functioning are significantly more pronounced in children prenatally exposed to alcohol than in children referred to psychiatric treatment who were not prenatally exposed. We explored the effect of alcohol exposure on social and adaptive functioning and explored whether or not social and adaptive functioning are significantly more impaired in children prenatally exposed to alcohol than in a clinical sample of children. METHODS: A sample of 33 alcohol-exposed children was compared with a sample of 33 clinic-referred nonexposed children. The groups were compared on measures of communication, daily living skills, and socialization. The groups were matched on sex, age, IQ, and outpatient or inpatient status. RESULTS: Analyses revealed that the prenatally alcohol-exposed children did not differ significantly from the nonexposed children in any of the domains of adaptive functioning. However, with age, exposed children showed a more rapid decline in socialization standard scores compared with the nonexposed clinical sample. CONCLUSIONS: Young children who were exposed to alcohol prenatally show deficits in all domains of adaptive functioning. Although these deficits do not seem to differ from those exhibited by young children with psychiatric problems but no prenatal exposure, deficits in socialization behavior of prenatally exposed children may become more significant with age.

Intensive care unit antimicrobial resistance and the role of the pharmacist.

Over the past 20 yrs, pharmacists have successfully integrated their services and expertise to gain acceptance as full members of pediatric, surgical, medical, and intensive care unit (ICU) patient care teams. The pharmacists' training in pharmacology, pharmacokinetics, pharmacodynamics, and pharmacoeconomics complements the expertise of other members of the patient care team. Generally, a strong background in infectious diseases and critical care also provides a focal point for clinical pharmacy service intervention. Although practitioners often focus on issues exclusively related to their specific hospital or ICU, the issues surrounding antibiotic resistance are more global and societal in nature. Medical, surgical, and pharmaceutical practices inside the hospital and ICU extend their influence into the community. Customs and practices of daily living in our society coupled with use of agents capable of altering microbial flora impact our hospital and ICU when patients from the community are admitted. The misuse of antibiotics and the lack of effective infection control programs are often identified as key components in the perpetuation of these phenomena. The focus for the pharmacist and the ICU team must be on the optimization of antibiotic use and infection control guidelines. This review will address the many issues that surround the appropriate use of antibiotics and what role the pharmacist can play in ensuring the optimal use of infection control measures in the ICU and hospital.

Retrospective analysis of cisapride-induced QT changes in end-stage renal disease patients.

BACKGROUND: This study involves a retrospective in-patient chart review of end-stage renal disease (ESRD) patients receiving haemodialysis to observe if cisapride significantly increases heart rate (HR), QT, and corrected QT (QTc) intervals on 12-lead electrocardiograms (ECGs). METHODS: Medical records for 23 patients who were being treated with chronic maintenance haemodialysis and had >/=2 ECGs while on cisapride and >/=2 ECGs while off cisapride were obtained and reviewed. HR, QT, and QTc on all 12-lead ECGs, reason for admission, and past medical history were analysed. RESULTS: A total of 529 ECGs (279 on/250 off cisapride) for 23 patients were included. The results, as calculated by each patient's individual averages (n=23), on vs off cisapride respectively, were HR, 88+/-14 vs 84+/-17 beats/min (P:=0.18); QT, 373+/-39 vs 382+/-45 ms (P:=0.24); and QTc, 443+/-27 vs 441+/-21 ms (P:=0.39). No significant difference was found in the number of admissions per month while on or off cisapride. No patient had an average QTc on or off cisapride that was >500 ms. One patient died from ventricular arrhythmia 12 days after discontinuing cisapride. The patient's QTc was significantly longer on vs off cisapride (487 vs 462 ms, P:=0. 007); however, this patient had an extensive cardiac history and multiple syncopal episodes prior to the use of cisapride. CONCLUSIONS: This study found no significant overall difference in HR, QT, and QTc interval or admissions/month on vs off cisapride in ESRD patients receiving haemodialysis.

Inappropriate therapy from atrial fibrillation and sinus tachycardia in automated implantable cardioverter defibrillators.

BACKGROUND: Inappropriate therapy from supraventricular tachyarrhythmias (atrial fibrillation [AF] and sinus tachycardia [ST]) in patients with implanted cardioverter defibrillators is a major challenge. We tested the performance of stability algorithms from 3 manufacturers for episodes of inappropriate therapy delivered because of AF and an onset algorithm for all episodes of inappropriate therapy caused by ST. METHODS: Therapy was classified as caused by ventricular tachycardia (VT), ST, or AF from review of stored intracardiac electrograms, history, clinical information, and R-R data before study inception. By using 30 to 60 R-R intervals before therapy, sensitivity and specificity for a family of stability values and percentage of onset values were calculated for each manufacturer and receiver operating characteristic curves generated. RESULTS: Of the 217 patients monitored, 62 (29%) received inappropriate therapy, and 40 had complete R-R information available. Of the 40 patients, 21 patients received therapy for AF, 19 for ST, and 1 patient for noise; 15 (38%) also received appropriate therapy for VT. We analyzed 83 episodes of VT from 18 patients, 94 episodes of AF from 21 patients, and 56 episodes of ST from 19 patients. Specificity, in the clinically relevant sensitivity range of >/=95%, was comparable across manufacturers at about 40%. An onset value of 80% was associated with 91% sensitivity and 95% specificity for the specific algorithm tested. CONCLUSIONS: Inappropriate therapy is a common problem in implantable cardiac defibrillators. The performance of the stability algorithms used to differentiate AF from VT was less than ideal, though comparable across manufacturers. The onset algorithm accurately differentiates ST from VT.

Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter-defibrillator. For the Worldwide Jewel AF Investigators.

BACKGROUND: To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion. METHODS AND RESULTS: We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing. CONCLUSIONS: A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.

Pharmacokinetics of pilocarpine in subjects with varying degrees of renal function.

Data from three separate single-center studies were combined to assess the pharmacokinetics of orally administered pilocarpine. Pilocarpine concentration-time data were used to generate a data set including 42 subjects (34 males, 8 females) with varying degrees of renal function (average of two estimated creatinine clearance rates of 10 to 112 mL/min). Age ranged from 19 to 88 years. Subjects received single oral doses (range: 2.5-20 mg) of pilocarpine. Plasma samples were collected at time 0; at 20 and 40 minutes; and at 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours following dose administration. Cmax and AUC were normalized to a 5 mg exposure in those subjects who received doses other than 5 mg. Plasma pilocarpine concentrations were determined by gas chromatography/mass spectrometry. The pharmacokinetic parameters (elimination rate constant, Cmax, tmax, AUC, Vd/F, and Cl/F) in subjects with impaired renal function were similar to results found in other pharmacokinetic studies involving normal healthy volunteers with only Cmax being significantly higher (p < 0.05). No significant regression relationships were noted between creatinine clearance and pilocarpine elimination rate constant, tmax, Vd/F, Cl/F, or AUC. Pilocarpine clearance does not appear to be impaired in patients with varying degrees of renal insufficiency.

The mythology of threshold variations as a function of electrode surface area.

It has been established that the chronic thresholds of cardiac pacing leads vary as a function of the (spherical) electrode's radius or (geometric) surface area and the thickness of fibrotic encapsulation. Where the radius of the electrode is equal to the thickness of the fibrous capsule (about 0.7 to 1 mm for polished surfaces), threshold should be at a minimum. Where the radius of the electrode is larger or smaller than the thickness of the fibrous capsule, then thresholds should increase since the electric field strength required to stimulate decreases as the square of the distance between the electrode's surface and stimulatable tissue. In addition, it has become (incorrectly) accepted that small electrodes do not sense well. About 8-mm electrodes, therefore, became the "standard" surface area, providing the best tradeoffs between pacing and sensing. Analysis of 18 years of canine data in our laboratory, however, suggest that these relationships may be overemphasized for the surface areas of clinical interest. In fact, new small porous and steroid-eluting electrodes do not have high thresholds, are efficient, and their sensing is excellent.