Intrathecal morphine plus general anesthesia in cardiac surgery: effects on pulmonary function, postoperative analgesia, and plasma morphine concentration

OBJECTIVES: To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery. INTRODUCTION: Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial. METHODS: Forty-two patients were randomized for general anesthesia (control group n=22) or 400 µg of intrathecal morphine followed by general anesthesia (morphine group n=20). Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC), forced expiratory volume (FEV), and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05). RESULTS: Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine group), with no significant decreases observed between groups. The two groups also exhibited similar results for FEV1 (p=0.085), FEV1/FVC (p=0.68) and PaO2/FiO2 ratio (p=0.08). The morphine group reported less pain intensity (evaluated using a visual numeric scale), especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001). Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037). The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL-1 and morphine group= 4.08 ng.mL-1, p=0.029). CONCLUSIONS: Intrathecal morphine administration did not ...

Determining plasma morphine levels using GC-MS after solid phase extraction to monitor drug levels in the postoperative period

OBJECTIVE: To implement a selective and sensitive analytical method to quantify morphine in small volumes of plasma by gas-liquid chromatography-mass spectrometry (GC-MS), aimed at post-operatively monitoring the drug. METHOD: A gas-liquid chromatographic method with mass detection has been developed to determine morphine concentration in plasma after solid phase extraction. Morphine-d3 was used as an internal standard. Only 0.5 mL of plasma is required for the drug solid-phase extraction in the Bond Elut-Certify®, followed by the quantification of morphine derivative by GC-MS using a linear temperature program, a capillary fused silica column, and helium as the carrier and make-up gas. The method was applied to determine morphine content in plasma samples of four patients during the postoperative period of cardiac surgery. Patient-controlled analgesia with morphine was performed by a venous catheter, and a series of venous blood samples were collected. After the oro-After the orotracheal extubation, morphine plasma levels were monitored for up to 36 hours. RESULTS: The run time was 16 minutes because morphine and the internal standard were eluted after 8.8 minutes. The GC-MS method had 0.5 -1000 ng/mL linearity range (r²=0.9995), 0.1 ng/mL limit of detection, intraday and interday precision equivalent to 1.9 percent and 6.8 percent, and 0.1 percent and 0.8 percent systematic error (intraday and interday, respectively). The analytical method showed optimal absolute (98 percent) and relative (100.7 percent) recoveries. Morphine dose requirements and plasma levels are discussed. CONCLUSION: The analytical gas-liquid chromatography-mass spectrometry method is selective and adequate for morphine measurements in plasma for applications in clinical studies.

Effect of morohine sulphate on total and triglycerides contents in serum and brai regions rat

The present work was undertaken to examine the effect of acute [35 mg/kg b.w.] and chronic [15-75 mg/kg b.w.] doses of morphine sulphate as well as withdrawal of the drug on total lipids and triglycerides levels in adult male albino rats [Ratus norvegicus] in an attempt to explore the changes occurring in serum levels and different brain regions. The data of the present work revealed occurrence of highly significant increases in total lipids of serum and different brain regions after acute and chronic administration of morphine and during drug withdrawal. The acute administration of morphine and during drug withdrawal led to significant increases in the triglycerides content of serum and in most the studied brain regions. On the other hand, after chronic administration of morphine, levels of triglycerides returned approximately to the normal values in serum, cortex, striatum and pons, while in cerebellum and thalamus- hypothalamus triglycerides level showed significant increases. Finally, the data presented here illustrate that morphine is capable of having a marked effect on lipids of serum and of different brain regions in rats

Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine) and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

Endogenous strychnine, nicotine, and morphine--description of hypo and hyper-strychninergic, nicotinergic and morphinergic state in relation to neuropsychiatric diseases.

Previous work from this laboratory had demonstrated the presence of endogenous morphine, strychnine and nicotine in the mammalian brain and human serum samples. Morphine is synthesised from tyrosine and strychnine and nicotine from tryptophan. This study examines the role of strychnine, nicotine and morphine in neuropsychiatric disorders. The blood levels of tyrosine, tryptophan, strychnine, nicotine and morphine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and tryptophan levels elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Nicotine was present in significant amounts in serum of patients with schizophrenia, CNS glioma and syndrome X with multiple lacunar state. Morphine was present in significant amounts only in the serum of patients with multiple sclerosis and MDP. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease and MDP. The presence of nicotine and strychnine in significant amounts could be related to elevated tryptophan levels suggesting the synthesis of these alkaloids from tryptophan. Morphine was not detected in most of the disorders owing to low tyrosine levels noted in them. Na(+)-K+ ATPase inhibition noticed in most of the disorders could be related to decreased hyperpolarising morphinergic transmission and increased depolarising nicotinergic and strychinergic transmission. The role of morphine, strychnine and nicotine in the pathogenesis of these disorders in the setting of membrane Na(+)-K+ ATPase inhibition is discussed.

Rapid analysis of some drugs of abuse in human blood by using EMIT and TLC techniques

A recent method for direct and rapid extraction of some drugs of abuse inwhole human blood was evaluated. Methanolic extraction of 2ml blood with 4mlmethanol yielded 0.3-3.5 ml clear extract after vigorous vortexing for 30seconds followed by centrifugation at 3000 rpm for 3 minutes. Analysis ofblood samples were done by using 2 techniques; Enzyme Multiplied Immunoassay[EMIT] and Thin Layer Chromatography [TLC] for the presence of morphine,amphetamine, phenobarbitone and methaqualone. The time taken from the startof the extraction procedure up to the point, at which the EMIT-apparatus wasinjected with the extract or TLC plates were spotted, was 10 minutes, i.e. rapid extraction. Values of detection of the four assayed drugs in the methanolic extract proved that this method of extraction is very sensitive and gives a potent, i.e. it can be used to detect drugs concentration ranges [subtherapeutic to therapeutic] for all assays

Certain morphologic changes in blood of starved rats during morphine injection

This investigation studied the effect of m.s. administration on cortisol level, alanine aminotransferase [CPT], aspartate aminotransferase [GOT], glucose and total protein in the sera of rats starved for a period of 1-6 days in comparison with control full nourished ones. The gained results showed that starvation of rats decrease GOT at 24 and 120 hours without any change in GPT level. Total protein and glucose were significantly decreased. Cortisol increased specially at last 4 days of starvation. M.s. injection resulted in a significant elevation of GPT at 48 hr and 120 hr and GOT at 48 hours of starvation. Glucose and total protein were significantly decreased at 24 and 120 hours. Serum cortisol level was elevated reaching the peak at 96 hours of starvation. Therefore, m.s. increase the metabolic changes produced by starvation

Morfina-Lidocaina intratecal y niveles sanguíneos de glucosa en pacientes / Intrathecal morphine-lidocaine and blood glucose levels in patients

Los efectos de la lidocaína o de morfina combinada con lidocaína sobre la glucosa sanguínea se evaluaron en un estudio doble-ciego y al azar en 19 pacientes a quienes se practicó prostatectomía transversal. Al grupo control se le administró lidocaína (100 mg). Al agregar morfina (1.0 ó 10 mg) a los grupos tratados, se produjo una leve caida en los niveles promedio de glucosa, P>0.05. Sin embargo, un paciente que recibió la dosis baja de morfina (1.0 mg), presentó una hipoglicemia severa, 1.1 mmol (20 mg%), que ocurrió 180 minutos después de la inyección intratecal. La similitud de su respuesta con la observada en animales, comprueba que este efecto importante de la morfina también sucede en el hombre. Se discute las implicaciones de tal hallazgo en relación con la farmacodinamia de los opiáceos. Se postula que la morfina activa un mecanismo de tipo encefalinérgico, descubierto recientemente, que es el encargado del paso intracelular de glucosa en los tejidos nerviosos. Se recomienda vigilar la glicemia en pacientes a quienes se administra morfina intratecal, no deben aplicarse dosis mayores de 1.0 mg en pacientes que no han desarrollado tolerancia a los opiáceos debido a la frecuencia alta de efectos colaterales severos.