Jens Kastrup

MEXILETINE FOR TREATMENT OF CHRONIC PAINFUL DIABETIC NEUROPATHY

Sixteen of nineteen patients completed a randomised double-blind crossover trial to assess the effect of oral mexiletine (10 mg/kg bodyweight daily) on the symptoms and signs of chronic painful diabetic neuropathy. The median age of the sixteen patients was 50 years (range 30-64). Assessment with a five-item clinical symptom scale showed significant improvement during the mexiletine phase compared with the placebo phase. Pain was reduced during mexiletine but not during placebo, as assessed by a visual analogue rating scale. Mexiletine treatment had no effect on tendon reflexes, vibration threshold levels, beat-to-beat variation in heart rate during deep breathing, and postural blood pressure response. Mild side-effects were seen in three of the sixteen patients during mexiletine treatment.

The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy

&NA; In a double‐blind controlled design, 7 patients with painful diabetic neuropathy received lidocaine 5 mg/kg or saline intravenously over a period of 30 min. Thermal sensibility quantified by thermotest was not affected by lidocaine. In 3 of the patients nociceptive flexion reflex thresholds could be determined. The threshold was increased by lidocaine and returned to pre‐infusion level within 10 days. Lidocaine also increased the threshold in 4 healthy subjects, but did not affect the Hoffmann reflex. These results suggest that lidocaine exerts its pain‐relieving effect on the spinal level in diabetic neuropathy.

Cerebral Blood Flow before and after Cardioversion of Atrial Fibrillation

In nine patients with atrial fibrillation (AF) of <3 months duration, CBF was measured the day before and after and again 30 days after electrical cardioversion therapy to sinus rhythm. The day before cardioversion therapy, median CBF (expressed as initial slope index 1, ml/100 g · min−1) was 35.8 and the day after it was 37.1. After 30 days in sinus rhythm, CBF was 39.4 (NS), although the end-tidal Pco2 values were lower than the pretreatment values. After correction for changes in end-tidal Pco2, the median CBF had increased significantly from 35.8 to 40.3 on day 1 and to 46.7 on day 30. The reduced CBF during AF could be a contributing factor in the development of cerebrovascular complications in patients with AF.

Dercum's disease (adiposis dolorosa). Treatment of the severe pain with intravenous lidocaine

Dercums disease (adiposis dolorosa) is associated with very painful subcutaneous fatty deposits normally localized to the lower extremities in which pain treatment is usually unsuccessful. Two patients with Dercums disease have been treated repeatedly with intravenous lidocaine for several months each time resulting in immediate pain relief for 8 and 25 days respectively. Placebo infusions did not provide pain relief. Hereafter, the patients were treated with peroral mexiletine and again had complete pain relief. We conclude that intravenous lidocaine or peroral mexiletine may be an effective analgesic treatment in patients with Dercums disease.

Chronic pain treatment with intravenous lidocaine

In a few uncontrolled studies intravenous lidocaine has been used in the treatment of chronic pain. In a controlled study we used intravenous lidocaine in 18 patients with severe chronic pain states due to various but mainly neurological diseases. After the infusion of lidocaine 14 patients (78%) had significant pain relief ranging from 2 hours to 25 days. There was no significant effect of placebo infusion with isotonic saline. The mechanism of the pain relieving ability of intravenous lidocaine is unknown.

Vibratory and thermal thresholds in diabetics with and without clinical neuropathy.

ABSTRACT Vibration and thermal detection threshold and heat pain threshold were determined in 34 diabetics scrutinized for clinical neuropathy using a standardized questionaire and examination form. On the basis of the clinical grading patients were classified as having either no neuropathy or a neuropathy of increasing severity. As expected thermal and vibratory detection threshold increased with increasing severity of neuropathy. Comparison between diabetics without symptoms and signs of neuropathy and a corresponding non‐diabetic control group showed that a warm sensibility index (WSI = the range in which non‐noxious heat is perceived) was significantly lower on feet in diabetics than in their matched non‐diabetic controls. The findings show that quantitative assessment of thermal sensitivity may be of value to detect early small nerve fiber dysfunction even in patients without symptoms or signs of a clinical neuropathy.

Impaired autoregulation of blood flow in subcutaneous tissue of long-term Type 1 (insulin-dependent) diabetic patients with microangiopathy: an index of arteriolar dysfunction

SummaryAutoregulation of blood flow in subcutaneous tissue was studied at the level of the lateral malleolus in eight long-term Type 1 (insulin-dependent) diabetic patients with clinical microangiopathy, eight short-term Type 1 diabetic patients without clinical microangiopathy and seven healthy control subjects. Blood flow was measured by the local 133Xenon washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevating to a maximum of 70 mmHg by head-up tilt; in the latter position venous pressure was kept constant and low by activation of the leg muscle vein pump (heel raising). Mean arterial blood pressure was thus varied between 60 and 160 mmHg. In normal and short-term diabetic subjects blood flow remained within 10% of control values during the changes in arterial blood pressure. In six of the eight Type 1 diabetic patients with clinical microangiopathy, autoregulation of blood flow was impaired, blood flow changing ap proximately 20% per 10 mmHg change in arterial blood pressure; the slope of the autoregulation curves was significantly higher compared with the two control groups (p<0.02). Resting mean arterial blood pressure was significantly elevated in long-term diabetic patients (median: 107 mmHg) compared with short-term diabetic (median: 85 mmHg) and control subjects (median: 91 mmHg) (p<0.01 and p<0.02, respectively). No correlation was, however, demonstrated between resting mean arterial blood pressure and the degree of disturbed autoregulation, but a relationship was demonstrated between the degree of disturbed autoregulation and the amount of periodic acid Schiff positive material in the terminal arteriolar walls of the investigated area (p<0.05).

Cerebral effects of scalp cooling and extracerebral contribution to calculated blood flow values using the intravenous 133Xe technique

With the intravenous 133Xe technique we measured cerebral blood flow (CBF) in eight healthy subjects during normal subcutaneous temperatures and during extracranial cooling. This gave rise to the possibility of evaluating the contribution of the extracerebral blood flow to the calculation of CBF values. With a two-compartmental analysis of the wash-out curves during cooling there was a significant reduction of the CBF indices f1, representing mainly fast blood flow in the grey matter and f2, representing blood flow in the slowly perfused white matter and extracerebral structures. The reduction of f1 was due to the slippage phenomenon:calculation of f1 was affected by a reduction in f2 due to a considerably reduced extracerebral blood flow. The initial slope index (ISI) calculated from 30 to 90 s of the first part of the presumed mono-exponential 133Xe wash-out curve was not affected by slippage as the ISI remained unchanged in spite of reduced extracerebral blood flow. It is concluded that CBF was unaffected by extracranial cooling. Extracranial cooling can be used to reduce the extracerebral blood flow contribution to the calculated CBF values.

A HPLC method for the simultaneous determination of disopyramide, lidocaine and their monodealkylated metabolites

This paper describes a simple high-performance liquid chromatographic method for the determination of disopyramide and lidocaine simultaneously with their dealkylated metabolites. After basic tert-butyl methyl ether extraction and back-extraction with phosphoric acid, the drugs and their metabolites were injected into a Supelcosil CN column and the absorbance of the eluate was measured at 215 nm. The sensitivity was 0.3 mumol/l and the obtained precision, selectivity and stability during storage were adequate for the performed clinical studies in patients therapeutically treated with disopyramide and/or lidocaine. Some results from the clinical studies are briefly presented.

Increased minimal vascular resistance and arteriolar hyalinosis in skin on the leg in insulin-dependent diabetic patients

Minimal vascular resistance (MVR) was determined in a paralysed cutaneous vascular bed at the dorsum of the foot in diabetic patients. Twelve long-term insulin-dependent diabetic (IDDM) patients with and nine short-term IDDM patients without nephropathy and retinopathy and eight control subjects were investigated. The vascular bed was paralysed by local injection of histamine. Skin perfusion pressure was varied by applying graded external counter pressure over the investigated area. Skin blood flow was measured by the local 99mTc wash-out technique before, during and after three to five step-wise increases of external counter pressure. The MVR was calculated from the reciprocal of the slope of the relationship between blood flow and applied pressure. The MVR was significantly increased in diabetic patients with (mean: 9.3 mmHg ml-1.100 g.min) and without nephropathy and retinopathy (8.5 mmHg ml-1.100 g.min) compared with non-diabetic subjects (5.2 mmHg ml-1.100 g.min) (p less than 0.001 and p less than 0.005, respectively). Diabetic microangiopathy (increased hyalinosis of the basement membranes in the terminal arterioles) was found in skin biopsies in nine of the 12 long-term IDDM patients and in four of the nine short-term IDDM patients, but not in the control subjects. Multiple regression analysis demonstrated a highly significant direct association between MVR and degree of diabetic microangiopathy in the same skin area (p less than 0.0002). A less significant direct association between MVR and arm diastolic blood pressure (p less than 0.05) and blood glucose concentration (p less than 0.05) was also found.(ABSTRACT TRUNCATED AT 250 WORDS)