A study comparing VVI and DDI pacing in elderly patients with carotid sinus syndrome.

OBJECTIVE: To determine whether single chamber ventricular demand (VVI) pacing is adequate for elderly patients with carotid sinus syndrome. DESIGN: Prospective double blind randomised cross over study. SETTING: Tertiary referral centre. PATIENTS: 30 consecutive patients aged over 60 years with carotid sinus syndrome referred for cardiac pacing. INTERVENTION: Patients underwent dual chamber pacemaker implantation and were then randomised to two three-month periods of VVI and DDI pacing. MAIN OUTCOME MEASURES: Responses to cardiovascular tests (vasodepression during carotid sinus massage, pacemaker effect, postural blood pressure measurements, and response to head up tilt), and symptoms. RESULTS: 11 patients developed profound hypotension during upright carotid sinus massage while pacing VVI compared with only two while pacing DDI. The upright pacemaker effect was greater in VVI (VVI, -31 (SD 19) mm Hg v DDI, -4 (12) mm Hg; P < 0.001). Postural blood pressure measurements and responses to head up tilt did not vary. Eleven patients were unable to tolerate VVI pacing and had to be withdrawn early from this limb of the study (group A). Fourteen of the remainder completed diary cards and did not express a preference (group B). No patient preferred VVI. Group A patients were older (group A, 78 (6) years v group B, 70 (9) years; P < 0.05), were more likely to be female (group A, 73% v group B, 14%; P < 0.01), and were more likely to have orthostatic hypotension while pacing DDI (group A, 46% v group B, 0%; P < 0.01). Group A and B patients could not be differentiated by other prepacing clinical or haemodynamic variables. CONCLUSIONS: Elderly patients with carotid sinus syndrome are likely to develop symptomatic hypotension following VVI pacing. The optimum pacing mode for individual patients cannot be predicted by simple cardiovascular tests before pacing.

Fludrocortisone in the treatment of hypotensive disorders in the elderly.

OBJECTIVE: To evaluate tolerance of fludrocortisone in older patients with hypotensive disorders. DESIGN: Prospective case series. SETTING: Syncope clinic. PATIENTS: 64 Consecutive patients over 65 years (mean age 80 years) with one or more hypotensive disorders (orthostatic hypotension, vasodepressor carotid sinus syncope, and/or vasodepressor neurocardiogenic syncope. INTERVENTIONS: Fludrocortisone in daily doses of 100 micrograms [corrected] (72%), 50 micrograms [corrected] (27%), and 200 micrograms [corrected] (one patient). MAIN OUTCOME MEASURES: Adverse events, treatment withdrawal. RESULTS: During follow up 13 patients died of unrelated causes. Of the remainder 33% discontinued fludrocortisone at a mean of five months. Reasons for discontinuing treatment were hypertension, five; cardiac failure, four; depression, three; oedema, three; and unspecified, two. In those who continued treatment supine systolic and diastolic blood pressure did not differ significantly from baseline (follow up two to 21 months). Hypokalaemia developed in 24% at a mean of eight months; in no case was treatment withdrawn because of hypokalaemia. CONCLUSION: Fludrocortisone, even in low doses, is poorly tolerated in the long term in older patients with hypotensive disorders.

Intravenous cannulation alters the specificity of head-up tilt testing for vasovagal syncope in elderly patients.

Prolonged head-up tilt is increasingly used as a diagnostic test for vasovagal syncope. Its sensitivity is reported to increase with the concurrent administration of intravenous isoprenaline. False-positive responses are common in young controls particularly following intravascular instrumentation. We studied the influence of intravenous cannulation alone on responses to head-up tilt in ten healthy elderly subjects. All remained asymptomatic during tilt when non-cannulated whilst five developed symptomatic hypotension following cannulation. Thus, intravascular instrumentation influences responses to held-up tilt in elderly subjects; the significance of positive responses obtained using intravenous isoprenaline in this age group requires further evaluation.

Pattern of inhibition of parasympathetic activity in response to incremental bolus doses of atropine in carotid sinus hypersensitivity.

Patients with established reproducible cardioinhibitory carotid sinus hypersensitivity were studied to define the dose of atropine required to abolish the heart rate slowing in response to carotid sinus massage, the heart rate response to the Valsalva manoeuvre and salivary gland flow. Bolus doses of intravenous atropine were given to a cumulative dose of 700 mcg. Cardioinhibition was abolished in all patients with a total dose of 700 mcg. The heart rate ratio during the Valsalva manoeuvre did not vary significantly. The decline in salivary gland flow was evident earliest, at a dose of 75 mcg. In clinical studies, 700 mcg of atropine will abolish the diagnostic cardioinhibitory response to carotid sinus message in patients with the syndrome. This may not prevent syncope, as could occur in the key frequent vasodepressor form of carotid sinus hypersensitivity syndrome.

Heart rate and blood pressure responses to carotid sinus massage in healthy elderly subjects.

The purpose of the study was to define heart rate and blood pressure responses to supine and upright carotid sinus massage in healthy elderly subjects and thus to establish the validity of current diagnostic criteria for carotid sinus syndrome in this age group. Twenty-five healthy asymptomatic subjects (61-87 years) had carotid sinus massage carried out following a standardized technique employing previously defined criteria for abnormal heart rate and blood pressure responses: 3 s asystole and a 50 mmHg fall in systolic blood pressure independent of any heart rate slowing (after intravenous atropine). No cardioinhibitory responses of greater than 3 s were documented. The mean maximal cardioinhibitory response was 1038 +/- 195 msec. Right-sided responses were more marked than left when upright (1040 +/- 202 vs. 946 +/- 135 msec; p < 0.01) but not when supine (1094 +/- 215 vs. 1073 +/- 194 msec; NS). After atropine three subjects (12%) had a significant vasodepressor response when upright, but none when supine. The mean maximal vasodepressor response was 21 +/- 14 mmHg. Right-sided blood pressure responses were more marked than left (p < 0.01). There was no fixed relationship between maximum heart rate slowing and the degree of vasodepression during massage (range 2-80 msec/mmHg). The diagnostic criteria for heart rate and blood pressure responses in carotid sinus syndrome are appropriate for supine carotid sinus massage in elderly subjects. Asymptomatic vasodepressor responses occur in a small proportion of healthy elderly when upright.

Clinical characteristics of vasodepressor, cardioinhibitory, and mixed carotid sinus syndrome in the elderly.

PURPOSE: Carotid sinus syndrome (CSS) is frequently overlooked as a cause of syncope in the elderly. It is diagnosed when carotid sinus massage (CSM) produces asystole exceeding 3 seconds (cardioinhibitory CSS), a reduction in systolic blood pressure exceeding 50 mm Hg independent of heart rate slowing (vasodepressor CSS), or a combination of the two (mixed CSS). Most published data pertain to the cardioinhibitory subtype. The recent availability of noninvasive phasic blood pressure monitoring has allowed accurate routine assessment of the vasodepressor response to CSM. The aim of this study was to assess the clinical characteristics of vasodepressor, cardioinhibitory, and mixed CSS. PATIENTS AND METHODS: CSM was carried out on 132 consecutive patients over 65 years referred for investigation of dizziness, falls, or syncope. Massage was performed both supine and upright with continuous electrocardiographic and phasic blood pressure monitoring. Patients exhibiting greater than 1.5-second asystole were given 600 micrograms of intravenous atropine to abolish heart rate slowing and allow assessment of the pure vasodepressor response. RESULTS: Carotid sinus hypersensitivity was documented in 64 patients (mean age 81 +/- 7 years, 31 male). The response was vasodepressor in 37%, cardioinhibitory in 29%, and mixed in 34%. Thirty-six patients had recurrent syncope, 17 presented with unexplained falls, and the remainder had dizziness alone. Symptoms had been present for a median of 24 months, and the median number of syncopal episodes was four. Twenty-five percent had sustained a fracture and, of these, 93% had not experienced a prodrome. Head movement precipitated symptoms in 47% and vagal stimuli in 73%. Episodes were unwitnessed in two thirds of patients. Twelve patients who presented with falls denied syncope but had witnessed loss of consciousness during CSM. Mean cardioinhibition was 5 +/- 2 seconds and mean vasodepression 61 +/- 9 mm Hg. The blood pressure nadir occurred rapidly at 18 +/- 3 seconds after massage, and baseline values were regained at 30 +/- 6 seconds. The clinical characteristics of patients with vasodepressor, cardioinhibitory, and mixed responses were similar. CONCLUSION: CSS is an underdiagnosed cause of dizziness, falls, and syncope in the elderly. The vasodepressor form occurs more frequently than previously reported and has clinical characteristics similar to those of the cardioinhibitory and mixed subtypes. Elderly patients with this condition may deny syncope and present with recurrent unexplained falls. CSM, ideally with noninvasive phasic blood pressure monitoring, should be routinely performed in elderly patients with unexplained bradycardic or hypotensive symptoms.

Off-line automated sample preparation--experience in a clinical drug investigation unit.

The authors describe an evaluation of the Du Pont Prep. off-line automatic centrifugal sample processing system, used in the authors' Drug Investigation Unit over the past two years. In comparison to liquid-liquid extraction, the authors found that assay precision has generally been improved, absolute recovery was quantitative, reliability has been good and the use of the system has resulted in notable labour saving. However, the cost per test based on a seven-year amortization of capital cost shows that the system is more expensive. Assays for urinary opiates, serum tricyclic antidepressants, serum isoxicam, serum valproate, serum metoclopramide and serum pindolol are presented and the merits of the method are compared with those for manual liquid-liquid extraction procedures.

Pharmacokinetics of two dosage levels of trimethoprim to 'steady-state' in normal volunteers.

Trimethoprim (TMP), previously available only with a sulphonamide, is now available alone. The kinetics of two dosage regimens (200 mg b.d. p o. and 300 mg o.d. p.o.) have been examined. The expected disposition of higher TMP concentrations following the initial dose of the 300 mg preparation is reversed when steady-state is reached, and is a function of dosage. The MIC of TMP for sensitive organisms in urine was greatly exceeded following both regimens and is the result of a favourable pH gradient. The serum concentrations at CSS (trough) following the 300 mg regimen did not consistently exceed the MIC for TMP, those for the 200 mg regimen were more satisfactory. The implications of these findings are that while both regimens would be satisfactory in the treatment of urinary tract infection the 200 mg regimen would be more appropriate for the treatment of infected sites where pH dependent accumulation of TMP does not occur.

Synergism between trimethoprim and sulfonamide in urine: does it exist?

In a randomized, crossover, multiple dose study, ten healthy volunteers received the recommended dosages of cotrimoxazole (80 mg trimethoprim and 400 mg sulfamethoxazole) and co-tri-famole (80 mg trimethoprim and 400 mg sulfamoxole) for five days each. Urinary levels of trimethoprim and each sulfonamide were measured daily for five days. The urinary ratios of trimethoprim and sulfonamide for both formulations were consistently lower than those considered optimal for synergy. Concentration of trimethoprim in the urine from both preparations was found to be greatly in excess of the MIC for trimethoprim-sensitive urinary pathogens (approximately 2 microgram/ml). The sulfonamide levels achieved were not consistently in excess of their MIC (approximately 200 microgram/ml) for either preparation.

Assay for trimethoprim in serum and urine by means of ion-pair chromatography.

We describe a rapid, precise, and reliable procedure for assay of trimethoprim in serum and urine by ion-pair chromatography. Trimethoprim concentrations in urine are determined by an externally standardized, direct-injection procedure; assay in serum involves a simple preliminary extraction and internal standardization. The assays are suitable for pharmacokinetic studies and have been applied to determination of trimethoprim concentrations in serum and urine during therapy with Co-trimoxazole, a sulfonamide/trimethoprim preparation.