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Biomedical subjects

P V Cole

Publications and source records attributed to P V Cole.

At least 19 recordsLinked to original sources

Decay of nitroprusside. I: In vitro.

The apparent intravascular decomposition of nitroprusside (SNP) has been attributed to photolysis and artefactual generation of cyanide (HCN) during assay, leading some workers to believe that large doses of SNP may be infused safely if light is excluded. However, we have shown that HCN is not produced from SNP during analysis. Significant amounts of HCN were formed only when SNP was first incubated with blood. The yield of HCN was a function of the temperature, pH and time of incubation. The time for release of 50% of the HCN from SNP 5 mumol litre-1 at 37 degrees C in blood was 26.6 min with greater than 90% yield in 2 h, and in plasma the optimum pH was about 7.5. A u.v. method for measuring SNP suggests that, at clinically appropriate blood concentrations, SNP is confined to plasma.

Ferricyanides↗

Decay of nitroprusside. II: In vivo.

Clinical experience suggests that nitroprusside (SNP) concentrations decay more rapidly in vivo than in vitro. Plasma concentrations of SNP were measured therefore in 20 patients at the end of an infusion, with mean arterial pressure (MAP) and cyanide (HCN) concentrations. Plasma SNP concentrations (20-243 micrograms litre-1; mean = 123.5 micrograms litre-1), were related to infusion rate (r = 0.66, P less than 0.001), and declined rapidly to a mean (SD) of 7.7 (4.5) micrograms litre-1 in 15 min. The decay of SNP correlated closely with the increase in arterial pressure (mean MAP vs log mean plasma SNP concentrations: r = -0.993, P less than 0.001), and was probably biphasic: mean (SD) T1/2 alpha = 0.89 (0.62) min, T1/2 beta = 14.3 (12) min. Mean plasma HCN and mean plasma SNP concentrations decreased together (r = 0.955, P less than 0.001), thus confirming that in vivo decomposition of the drug is the source of HCN.

Adult↗

Quantitative EEG and brainstem auditory evoked potentials: comparison of isoflurane with halothane using the cerebral function analysing monitor.

We studied EEG and brainstem auditory evoked potentials (BAEP) during routine surgery at various concentrations of isoflurane (12 patients) or halothane (11 patients) or during prolonged (mean 2.5 h, range 1.9-3.5 h) administration of 1% isoflurane (five patients). Recording and analysis was performed with the cerebral function analysing monitor (CFAM). At equivalent MAC, the two agents exhibited distinctive neurophysiological profiles. Increasing concentrations of isoflurane produced a clear sequence of EEG changes (decreasing fast and increasing slow components) then burst suppression activity suggesting cortical depression. With halothane, changes in EEG amplitude were less pronounced and those in frequency content less systematic, with no periods of suppression. Simultaneous BAEP showed greater latency increase with halothane than with isoflurane. Prolonged administration of 1% isoflurane was associated with a stable EEG (no periods of suppression) and BAEP.

Adult↗

Isoflurane prevents EEG depression during trimetaphan-induced hypotension in man.

We have studied the EEG analysed with the cerebral function analysing monitor (CFAM) during trimetaphan (TMP)-induced hypotension to a mean arterial pressure (MAP) of 40 mm Hg in 20 normocapnic patients anaesthetized with either 1% end-tidal isoflurane or 0.5% halothane. During the acute reduction in MAP, the average reduction in mean EEG amplitude with halothane was 14%, two patients showing short periods of EEG suppression; the decline in EEG amplitude correlated with declining MAP in four patients. In contrast, the average reduction in mean EEG amplitude with isoflurane was only 0.3% and there were neither periods of suppression nor any correlation between EEG amplitude and MAP. No significant changes in EEG frequency occurred in either group. Isoflurane prevented EEG amplitude depression during TMP-induced hypotension.

Adult↗

Cardiovascular actions of trimetaphan nitroprusside. Comparison with sodium nitroprusside in greyhounds.

Trimetaphan nitroprusside (TNP) is a new potent hypotensive agent developed to induce and maintain decreases in arterial pressure unaccompanied by resistance. This study investigated its properties and compared them with those of sodium nitroprusside (SNP) in anaesthetized greyhounds. The mean dose response to TNP was obtained by measuring haemodynamic changes in five dogs. With increasing doses, stepwise decreases in mean arterial pressure and progressive increases in heart rate occurred: cardiac index did not change significantly. In a further six greyhounds, SNP and TNP were alternately infused to induce and maintain a 30% reduction in arterial pressure for 30 min. Both drugs were short-acting, decreased systemic vascular resistance and caused tachycardia. Infusion of TNP produced lower plasma and red cell cyanide concentrations; SNP maintained hypotension with significantly less tachycardia. We conclude that there was no outstanding advantage of TNP over SNP when given as a short-term infusion in greyhounds.

Anesthesia, General↗

Nalbuphine combined with midazolam for outpatient sedation. An assessment of safety in volunteers.

Eighteen healthy volunteers were studied in a double-blind trial to determine which dose of nalbuphine (0.05, 0.1 or 0.2 mg/kg) may be combined with midazolam 0.05 mg/kg to provide a safe outpatient intravenous sedative technique. The ventilatory response to carbon dioxide and end tidal PCO2 were measured before and after the drugs were administered. A mild degree of respiratory depression occurred, which was maximal at 3-30 minutes after injection. This was not related to dose except that nalbuphine 0.05 mg/kg resulted in the slowest respiratory rates. The implications of these findings for clinical practice are discussed.

Adult↗

Nalbuphine combined with midazolam for outpatient sedation. An assessment in fibreoptic bronchoscopy patients.

Forty patients who required day case fibreoptic bronchoscopy were sedated with either nalbuphine 0.2 mg/kg and midazolam 0.05 mg/kg (n = 20), or midazolam 0.05 mg/kg alone (n = 20). Extra midazolam was administered when required. The degree of respiratory depression measured by arterialised venous carbon dioxide levels was recorded together with heart rate, arterial blood pressure, respiratory rate and sedation score, before administration of the drugs and at regular intervals thereafter. Patients who received nalbuphine had slightly higher carbon dioxide levels but respiratory rate and cardiovascular changes were similar in both groups. The addition of nalbuphine to midazolam improves the quality of sedation but prolongs the recovery time and increases the incidence of side effects.

Ambulatory Care↗

Sodium thiosulphate decreases blood cyanide concentrations after the infusion of sodium nitroprusside.

Plasma and red cell cyanide, and plasma thiocyanate, concentrations were measured in 30 patients undergoing elective nitroprusside-induced hypotension. One randomly selected group (n = 15), who received 0.21-0.70 mg kg-1 over periods of 50-160 min, were given a bolus of sodium thiosulphate 10.6-38.5 mg kg-1 immediately on cessation of the nitroprusside administration. The other group, who received infusions of 0.11-0.85 mg kg-1 for periods of 59-197 min, received no antidote. Cyanide concentrations, expressed as a percentage of the immediate post-infusion values, were significantly lower in the treated group in all subsequent blood samples (at 10, 30 and 60 min; plasma cyanide P less than 0.05; red cell cyanide P less than 0.001). Improved cyanide metabolism was further demonstrated by a sharp increase in mean plasma thiocyanate concentration (P less than 0.05) in the group receiving the antidote.

Adult↗

Toxicity of bone marrow in dentists exposed to nitrous oxide.

The morphology of the bone marrow of 21 dentists who habitually used nitrous oxide in their surgeries was investigated. Exposure to nitrous oxide was measured with an atmospheric sampling device, and each dentist was invited to fill in a questionnaire giving details of medical history, diet, and intake of alcohol. During the trial a full neurological and haematological investigation was carried out and a bone marrow aspirate was examined both morphologically and by the deoxyuridine suppression test. Mean exposures to nitrous oxide ranged from 159 to 4600 parts per million. In all subjects serum vitamin B12 and folate concentrations were within normal limits. Abnormal results of deoxyuridine suppression tests were obtained in three of the 20 dentists tested; two of these three had abnormal white cells in their peripheral blood films. This study provides direct evidence that occupational exposure to nitrous oxide may cause depression of vitamin B12 activity resulting in measurable changes in bone marrow secondary to impaired synthesis of deoxyribonucleic acid.

Anesthesia, Dental↗

Electrical activity of the cerebral cortex during induced hypotension in man. A comparison of sodium nitroprusside and trimetaphan.

During the routine use of controlled hypotension the electroencephalogram (EEG) and mean arterial pressure (MAP) were monitored in 20 normotensive patients (younger than 70 years-of-age) receiving either trimetaphan (TMP) or sodium nitroprusside (SNP). The reduction in MAP was quicker and greater with SNP. Significant differences in EEG voltage between the two agents were seen in the range 55-40 mm Hg, electrical activity being better maintained with SNP. However, all patients showed some decline in EEG voltage with hypotension and half of these showed significant correlations with MAP. These pressure-dependent cerebral effects were not predictable in terms of age, preoperative arterial pressure or hypotensive agent. Our work supports previous experimental evidence that, during more profound hypotension, cerebral electrical activity is better maintained with SNP than with TMP. A simple measure of total EEG power, or filtered EEG voltage envelope (CFM) was shown to be a more useful monitor of cerebral electrical activity during controlled hypotension than measurements of power distribution in different frequency bands.

Adult↗

Blood cyanide and thiocyanate concentrations produced by long-term therapy with sodium nitroprusside.

Blood cyanide (HCN) or plasma thiocyanate (SCN) concentrations, or both, were measured in 30 patients (ages 11 months-72 yr) receiving sodium nitroprusside (SNP) for 12-314 h. Sequential measurements in three of these patients (infused 5, 12 and 13 days) showed that HCN concentrations varied with dose rate, while SCN concentrations increased linearly with increasing SNP dose. The accumulated data confirmed that the rate of administration (0.3-6.5 micrograms kg-1 min-1) determined the plasma HCN concentrations (0-3.8 mumol litre-1; y = 0.267 X -0.0733; r = 0.64; n = 51; P less than 0.001). Thus, if prolonged exposure to plasma HCN concentrations greater than 1 mumol litre-1 is to be avoided, the maximum safe sustained dose rate of SNP will lie near to 4 micrograms kg-1 min-1. Likewise, the SCN results (30--880 mumol litre-1) confirmed the close relationship between plasma concentrations and the total SNP dose (0.44-32.9 mg kg-1; y = 24.6x + 74.9; r = 0.95, n = 51, P less than 0.001). Therefore, we suggest that, to avoid SCN toxicity (plasma SCN greater than 1.75 mumol litre-1), in the absence of SCN monitoring, the total SNP dose should be less than 70 mg kg-1 in patients with normal renal function.

Adolescent↗

The antidotal action of thiosulfate following acute nitroprusside infusion in dogs.

The authors previously demonstrated in dogs that a bolus dose of sodium thiosulfate maintained enhanced cyanide metabolism throughout a 1-h infusion of sodium nitroprusside (SNP). To further test this antidotal action, a bolus dose of thiosulfate (150 mg . kg-1) was given to eight dogs at the end of a 60-min near-lethal infusion of nitroprusside (3 mg . kg-1). Within 2 min of the antidote, mean plasma thiocyanate levels (70.3 mumol . l-1) were significantly higher than those of seven control dogs given nitroprusside only (45.9 mumol . l-1, P = 0.002) and plateaued at 153.8 mumol . l-1 within 60 min, while the control values only reached 79.1 mumol . l-1 (P less than 0.001). Although differences between plasma cyanide levels in the two groups only attained significance 1 h after administering the antidote (0.8 vs. 2.74 mumol . l-1, P = 0.03), red blood cell cyanide concentrations were significantly lower in the antidote group within 5 min (166 vs. 225 mumol . l-1, P = 0.004) and remained so throughout the 2-h observation period. Compared with the controls, there was an impressive reduction in mean half-lives of plasma cyanide (25.1 vs. 74.1 min) and red blood cell cyanide (22.4 vs. 203.6 min). Similarly, peak cyanide levels occurred much sooner following the antidote (mean times: plasma cyanide 2.9 vs. 5.9 min; red blood cell cyanide 0.25 vs. 11 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Imbalance↗

Blood carboxyhaemoglobin, plasma thiocyanate, and cigarette consumption: implications for epidemiological studies in smokers.

Carboxyhaemoglobin and plasma thiocyanate concentrations were found to be significantly correlated with self-reported daily cigarette consumption in 360 smokers (r = 0.416 and 0.412 respectively; p less than 0.001). The extent to which inhalation patterns affected the intake of cigarette smoke constituents was determined from the partial correlation between carboxyhaemoglobin and plasma thiocyanate concentrations after the number of cigarettes smoke per day had been allowed for (r = 0.48). Thus 23% of the variation in carboxyhaemoglobin and thiocyanate concentrations was accounted for by the was a cigarette was smoked and a further 21% by the number smoked a day. Furthermore, the relation between carboxyhaemoglobin or plasma thiocyanate and daily cigarette consumption was not linear but reached an asymptote at consumption rates above 25 cigarettes a day. These results suggest that by itself daily cigarette consumption will not identify those smokers most at risk and will also underestimate and dose-response relationship between smoking and selected diseases.

Carboxyhemoglobin↗

Carboxyhaemoglobin and plasma thiocyanate: complementary indicators of smoking behaviour?

Carboxyhaemoglobin and plasma thiocyanate concentrations were measured in 79 non-smokers and 360 cigarette smokers. The mean levels were 0.73% and 7.09% carboxyhaemoglobin and 40 . 2 and 133 . 8 mumol thiocyanate/1 plasma respectively. With 1 . 6% carboxyhaemoglobin and 73 . 0 mumol thiocyanate/1 plasma as critical values the concentrations of carboxyhaemoglobin in 96.6% of subjects and of thiocyanate in 93.4% were compatible with reported smoking status. This difference between the two tests is significant (p less than 0 . 005). Statistical combination of the carboxyhaemoglobin and thiocyanate results, with the use of linear discrimination analysis, only marginally improved their diagnostic efficiency (96.8% of subjects were grouped correctly). This analysis did, however, successfully regroup 21 of 26 individuals with contradictory carboxyhaemoglobin and thiocyanate classifications. It is concluded that in this study determination of thiocyanate added little to the information obtained from carboxyhaemoglobin measurements alone.

Adult↗

Simple and rapid method for the assessment of the oxygen affinity of haemoglobin.

The affinity of haemoglobin for oxygen may be expressed as the oxygen tension at 50% saturation under standard conditions (P50). A rapid technique for the determination of P50 using a micro-tonometer with pH electrode and oximeter was evaluated. Equilibration time was found to be 15 minutes with no change in PCV, although plasma haemoglobin levels were slightly elevated. Estimation of P50 in blood from 32 non-smokers gave a mean of 26.4 +/- 0.9 (SD) mm Hg (3.51 +/- 0.12 kPa) with a precision of 0.3 (SD) mm Hg (0.04 kPa). The system was found to be accurate, precise, and simple in operation, allowing up to 16 P50 determinations an hour to be performed with 85 microliters blood samples.

Hematocrit↗

Smoking and arterial reconstruction.

Fasting levels of serum triglyceride, serum cholesterol, lipoprotein, uric acid, fibrinogen and carboxyhaemoglobin (COHb) were measured in 64 patients with stenosing arterial disease before reconstructive surgery, and were compared with those for normal, age- and sex-matched controls. All except fibrinogen were significantly higher in the patients with arterial disease than in the controls. The outcome of arterial reconstruction, assessed both clinically and by Doppler pressure measurement, was compared in terms of these risk factors. The reconstruction of 12 patients failed between 3 months and 5 years, leaving 52 patients with patent reconstructions at the end of the follow-up period. There was no difference between the two groups in terms of any of the risk factors, except for COHb. The COHb level (associated with inhalation of cigarette smoke) was significantly higher in the reconstruction failure group than in the reconstruction success group. We believe that patients should stop smoking cigarettes before reconstructive arterial surgery is undertaken.

Arterial Occlusive Diseases↗