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Biomedical subjects

M A Marcus

Publications and source records attributed to M A Marcus.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacological considerations during pregnancy.

We present a brief overview of recent literature concerning some of the drugs used in pregnancy, labour and delivery. Obstetric anaesthesia continues to evolve through the reuse of old drugs such as magnesium sulphate or the manipulation of current drugs (e.g. propofol for emesis) in order to improve patient outcome. Pregnant women have traditionally been therapeutic orphans. The use of new agents such as levobupivacaine and ropivacaine in obstetric patients lags behind that of their non-pregnant counterparts. However, this gap is decreasing and these new drugs offer benefits to the parturient woman.

Journal Article↗
PubMed2000

Acute pain management: analysis, implications and consequences after prospective experience with 6349 surgical patients.

An acute pain service (APS) was set up to improve pain management after operation. We attempted to reduce the length of stay in the intensive care unit (ICU) of patients undergoing major surgery and to improve their homeostasis and rehabilitation using a multimodal approach (pain relief, stress reduction, early extubation). Patient-controlled epidural analgesia (PCEA) was a keystone of this approach. If PCEA was not applicable, patients received patient-controlled intravenous analgesia (PCIA) instead. Brachial plexus blockade (BPB) was used for surgery of the upper limbs. A computer based documentation system was used to help evaluate prospectively (a) the quality of analgesia, (b) adverse effects and risks of the special pain management techniques, and (c) cost-effectiveness. Patients receiving PCEA (n = 5.602) received a patient-titrated continuous infusion into the epidural space of either bupivacaine 0.175% or ropivacaine 0.2%, with 1 microg sufentanil mL(-1) added, followed by patient-controlled boluses of 2 mL (lockout time 20 min). For patients receiving PCIA (n = 634) an initial bolus of 7.5-15 mg piritramide was given, and the subsequent bolus was 2 mg (lockout time 10 min). A continuous infusion of bupivacaine 0.25% was administered to patients receiving BPB (n = 113). The dose was titrated to a dynamic visual analogue scale (VAS) scores < 40. The mean treatment periods were: BPB = 4.33 days, PCEA = 5.6 days, PCIA = 5.0 days. In the case of PCEA, the quality of pain relief, vigilance and satisfaction were superior compared with the PCIA method, which resulted in greater sedation and nausea. Although personal supervision was higher for the PCEA-treated patients, cost analysis revealed final savings of Euro 91,620 for the year 1998 obviating the need for an ICU stay totalling 433 days. Provided that PCEA is part of a fast-track protocol employing early tracheal extubation and optimal perioperative management, the associated initial higher costs will be recouped by the benefits to patients of better pain relief after surgery and fewer days subsequently spent in the ITU.

Amides↗
PubMed2000

What concentration of sufentanil should be combined with ropivacaine 0.2% wt/vol for postoperative patient-controlled epidural analgesia?

UNLABELLED: In this randomized double-blinded study, we sought to determine an optimal dose-combination of sufentanil with ropivacaine 0.2% wt/vol as postoperative epidural analgesics. One hundred twenty patients undergoing major abdominal surgery under general and thoracic epidural anesthesia (T9-11) were assigned to groups receiving patient-controlled epidural analgesia with ropivacaine 0.2% wt/vol (R), ropivacaine 0.2% wt/vol + sufentanil 0.5 microg/mL (R+S0.5), 0. 75 microg/mL (R+S0.75), 1.0 microg/mL (R+S1). A visual analog score of less than 40 was considered effective, and all side effects were recorded. In randomized subgroups (10 patients per group), plasma pharmacokinetic data were obtained for both epidural drugs. Four patients in Group R and two in Group R+S0.5 were excluded because of inadequate analgesia. The drug infusion rates (range of means: 5.4-5. 9 mL/h) were similar in all patients. Analgesia was superior for sufentanil 0.75 microg/mL with no further enhancement by the larger sufentanil concentration of 1 microg/mL. Sufentanil plasma levels were within the range of the minimal effective concentrations (highest in R+S1), and there was no covariation between plasma levels and pain relief. Free ropivacaine plasma concentrations remained stable for 96 h. No severe side effects were detected, although pruritus correlated with an increasing dose of sufentanil. We conclude that the combination of ropivacaine 0.2% wt/vol and 0.75 microg/mL sufentanil provided the best analgesia with the fewest side effects of the three combinations tested. IMPLICATIONS: Sufentanil is added to epidural infusions of ropivacaine 0.2% wt/vol to improve the effectiveness of postoperative pain management. Regarding the risk of side effects, however, it is still unclear what concentration of sufentanil should be added to the local anesthetic. For postoperative thoracic epidural analgesia after major abdominal surgery, the combination of ropivacaine 0.2% wt/vol and 0.75 microg/mL sufentanil resulted in an appropriate cost:benefit ratio between good analgesia and side effects.

Adult↗
PubMed2000

Fetal surgery: general or regional anaesthesia?

Major improvements in the diagnosis and treatment of fetal malformations, including in-utero surgical repair, have occurred in the past decade. As opposed to anaesthesia for caesarean sections, a high placental drug transfer is warranted to provide adequate fetal anaesthesia and immobility, strongly favouring the use of general anaesthesia for these cases. Even though the question of fetal pain perception is still debated, studies suggest that attenuation of the fetal stress response can improve outcome. Other major concerns include the maintenance of uterine blood flow and uterine relaxation, as premature labour and delivery severely limit fetal benefits from surgery. When performing these procedures, physicians have a special responsibility to weigh maternal risks against fetal benefits and should not jeopardize the life of the mother for procedures with questionable fetal outcome.

Journal Article↗
PubMed1999

Insulin sensitivity and serum triglyceride level in obese white and black women: relationship to visceral and truncal subcutaneous fat.

Although independent associations of visceral fat with the insulin resistance syndrome were previously reported in obese women, the importance of truncal subcutaneous fat with regard to insulin sensitivity is still controversial. We measured the insulin sensitivity index (S(I)), serum triglyceride (TG) level, and regional fat by two methods: (1) the sum of five truncal and four peripheral skinfolds (TrSUM and PerSUM) in 38 white and black obese nondiabetic premenopausal women, and (2) abdominal visceral (VFM) and subcutaneous fat mass (AbdSCFM) by a combination of magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA) in a subset of 26 of these women. After adjusting for the total body fat mass, TrSUM and VFM were independently and negatively related to S(I) (n = 38, P < .012 and n = 26, P < .035, respectively), whereas PerSUM and AbdSCFM were not related (P > .50). Based on multiple regression modeling, TrSUM significantly predicted S(I) independently of the VFM (n = 26, P < .001). Black women had lower S(I) at all levels of TrSUM (n = 38, P = .061 for the slope and P = .03 for the intercept of the regression lines). After adjusting for the total body fat mass, only VFM showed an independent positive relation to serum TG, and race did not affect this relationship (n = 26, P < .001). In conclusion, (1) we confirmed the independent association of the VFM with insulin resistance and elevated TG in obese women; (2) the AbdSCFM measured by a combination of MRI and DXA did not show an independent association with S(I) in obese women; and (3) the independent association of TrSUM with S(I) suggests that truncal subcutaneous fat depots contribute to insulin resistance in obese women independently of the degree of visceral fat.

Absorptiometry, Photon↗
PubMed1999

Thermal and mechanical antinociceptive action of spinal vs peripherally administered clonidine in the rat inflamed knee joint model.

It has been demonstrated recently that in addition to its spinal analgesic actions, the alpha 2 adrenoreceptor agonist clonidine also has peripheral analgesic activity. Few data are available regarding the antinociceptive effects of spinal vs peripherally delivered clonidine in inflammatory pain. Thus we have studied spinal (intrathecal = i.t.) and peripheral (intra-articular = i.a.) administration of clonidine in the rat inflamed knee joint model. Thermal and mechanical antinociception was assessed in rats over 28 h using a modified Hargreaves box and von Frey hairs after induction of tonic persistent inflammatory pain by injection of a kaolin-carrageenan mixture into the right knee joint. Thirty minutes after injection of kaolin-carrageenan, clonidine was administered via an i.t. catheter or by i.a. injection into the right inflamed knee joint or by subcutaneous injection (s.c.) (highest effective intra-articular dose). The specific site of action was assessed using the alpha 2 antagonist yohimbine i.t., i.a. or s.c. Clonidine i.t. resulted in thermal and mechanical antinociception during ongoing inflammation, which was not enhanced by inflammation. In contrast, i.a. delivery of clonidine, which also produced a dose-dependent thermal and mechanical antinociceptive effect, revealed a leftward shift in the antinociceptive activity produced by ongoing inflammation. Yohimbine inhibited the antinociceptive action of clonidine at the site of delivery. We suggest that clonidine produces potent thermal and mechanical antinociception regardless of the route of administration. However, chronic inflammatory processing appears to enhance the antinociceptive efficacy of the peripheral alpha 2 agonist.

Adrenergic alpha-Agonists↗
PubMed1999

Epidural analgesia with local anesthetics after abdominal surgery: earlier motor recovery with 0.2% ropivacaine than 0.175% bupivacaine.

UNLABELLED: The aim of this prospective, randomized, double-blinded study was to compare pain relief, side effects, and ability to ambulate during epidural anesthesia with ropivacaine 0.2% plus sufentanil versus bupivacaine 0.175% plus sufentanil after major gastrointestinal surgery. Epidural catheters were inserted at T8-11, and 30 microg of sufentanil with 15 mL of ropivacaine 0.75% (Group 1, n = 42) or bupivacaine 0.5% (Group 2, n = 44) was injected. General anesthesia was induced, a continuous epidural infusion (5 mL/h) was then begun with 1 microg/mL sufentanil plus ropivacaine 0.2% (Group 1) or bupivacaine 0.175% (Group 2). Postoperatively, the infusion rate was adjusted to individual requirements. Patients were also able to receive additional 2-mL bolus doses every 20 min. Demographic data (except for gender and height), analgesia, drug dosage, and side-effects, including motor blockade (Bromage score), were similar in both groups, but mobilization recovered more quickly in Group 1. Gender, age, ASA physical status, duration of surgery, and intraoperative blood loss had no effect on mobilization. We conclude that epidural analgesia is effective and safe with both regimens. There is not necessarily a correlation between the Bromage score and the desired outcome of mobilization. The ability to walk postoperatively is hastened if ropivacaine is used instead of bupivacaine. IMPLICATIONS: Regarding pain relief and side effects, epidural analgesia with ropivacaine 0.2% and sufentanil 1 microg/mL yields pain scores and pain intensity comparable to those for the well evaluated combination of bupivacaine 0.175% and sufentanil 1 microg/mL. However, earlier recovery of the ability to walk unassisted in patients receiving the combination of ropivacaine and sufentanil may result in their earlier rehabilitation.

Abdomen↗
PubMed1998

Haemodynamic effects of repeated epidural test-doses of adrenaline in the chronic maternal-fetal sheep preparation.

A randomized crossover study was designed using the chronically instrumented pregnant sheep preparation to study the possible effects of epidural injection of adrenaline as a single compound on the circulation of mother and fetus. Three consecutive identical doses of adrenaline were administered epidurally with a 30 min interval between treatments. In a randomized crossover fashion two dosages (10 and 15 micrograms) were tested on different days. The day after the last epidural experiment the same doses of adrenaline were given intravenously (i.v.). Between the two i.v. doses a 30 min interval was allowed for values to return to baseline. Twenty-seven experiments were performed in eight ewes. Epidural administration of adrenaline did not affect maternal mean arterial pressure, maternal heart rate, uterine blood flow, fetal mean arterial pressure, fetal heat rate, or maternal and fetal blood gases and acid-base status. After i.v. administration of adrenaline the uterine blood flow decreased in a dose-dependent fashion, but the other haemodynamic variables were not affected. In conclusion, this study indicates that consecutive epidural injections of adrenaline have no significant effect on maternal and fetal haemodynamic responses, uterine blood flow, blood gases and acid-base status in the gravid ewe. However, an i.v. injection of 10 or 15 micrograms adrenaline decreases the uterine blood flow and could compromise the fetus.

Acid-Base Equilibrium↗
PubMed1998

The effects of adding isoproterenol to 0.125% bupivacaine on the quality and duration of epidural analgesia in laboring parturients.

UNLABELLED: This study was conducted to determine the effects of adding isoproterenol to epidural bupivacaine and sufentanil on the quality and duration of analgesia during labor. In a double blind, randomized study, 80 women were divided into two groups, receiving three doses of 0.125% bupivacaine with 7.5 microg of sufentanil and either 12.5 microg of epinephrine (EPI group) or 5 microg of isoproterenol (ISO group). Contraction pain was measured using a 100-mm visual analog scale (VAS) before epidural analgesia, at 5-min intervals for 15 min after each epidural injection, and hourly thereafter. Overall, no significant differences were observed in VAS scores between the groups. However, in the ISO group, VAS scores at 10 and 15 min after the first and second administration were significantly lower than those in the EPI group. Analgesia after each administration lasted significantly longer in patients who received epinephrine. Because of the limited duration of analgesia in the ISO group, more patients in this group received a fourth epidural administration of 0.125% bupivacaine with epinephrine 1:800,000. In conclusion, the addition of isoproterenol to bupivacaine and sufentanil induces a faster onset of analgesia and reduces the duration of analgesia compared with bupivacaine with sufentanil and epinephrine. Therefore, it is preferable to use isoproterenol only once, as a test dose, after the placement of the epidural catheter. IMPLICATIONS: We analyzed the quality and duration of analgesia in laboring women after they received bupivacaine and sufentanil combined with isoproterenol or epinephrine epidurally. We found that the addition of isoproterenol to bupivacaine and sufentanil induces a faster onset of analgesia and reduces the duration of analgesia.

Adrenergic beta-Agonists↗
PubMed1998

Central and peripheral analgesia mediated by the acetylcholinesterase-inhibitor neostigmine in the rat inflamed knee joint model.

UNLABELLED: Intrinsic cholinergic inhibitory pathways present a key modulating system in pain perception. The use of intrathecal (i.t.) acetylcholinesterase-inhibitors, such as neostigmine, result in analgesia in both preclinical and clinical models. However, whether i.t. neostigmine suppresses tonic persistent pain or has peripheral sites of antinociceptive action has not been determined. Thus, we studied central (i.t.) and peripheral (intraarticular; i.a.) neostigmine in a rat inflamed knee joint model. Inhibition of thermal and mechanical hyperalgesia was assessed over 28 h using a modified Hargreaves box and von Frey hairs, respectively. I.t. neostigmine resulted in a dose-dependent thermal analgesia (50% of maximal effective dose [ED50] 0-4 h: 6.6 microg, 24-28 h: 9.4 microg) and mechanical analgesia (ED50 0-4 h: 3.5 microg, 24-28 h: 4.3 microg). I.t. atropine reversed analgesia by i.t. neostigmine. I.a. neostigmine also resulted in an i.a. atropine reversible dose-dependent increase of thermal analgesia, although it did not exceed 60% of a maximal possible analgesic effect with the largest applied dose (ED50 0-4 h: 76.2 microg, 24-28 h: 140.1 microg). Partial suppression of mechanical hyperalgesia was observed after i.a. neostigmine. We conclude that centrally administered neostigmine modulates thermal and mechanical antinociception in this animal model of inflammatory pain. These data suggest a peripheral site of muscarinic antinociception. IMPLICATIONS: This animal study shows that administration of the acetylcholinesterase-inhibitor neostigmine results in enhanced levels of the endogenous neurotransmitter acetylcholine, which seems to act as one of a group of analgesia-modulating compounds at central and peripheral sites in inflammatory pain.

Analgesics, Non-Narcotic↗
PubMed1997

Anthropometrics do not influence dual X-ray absorptiometry (DXA) measurement of fat in normal to obese adults: a comparison with in vivo neutron activation analysis (IVNA).

Dual-energy X-ray absorptiometry (DXA) is now a commonly used method for the determination of bone mineral status and body composition in humans. The purposes of this study were to compare fat mass by in vitro neutron activation analysis (FMIVNA) with that by DXA (FMDXA) in an anthropometrically heterogeneous sample of healthy adult men (n = 33) and women (n = 36) (19 < or = BMI < or = 39), and to determine whether differences in fat mass estimates between the two methods (delta FM) were attributable to subject anthropometry as defined by several circumference (waist, iliac crest, thigh) and skinfold thickness (umbilical, suprailiac, abdominal) measurements. No significant differences between FMDXA and FMIVNA were observed in men (p = 0.46) or women (p = 0.09). The two methods were very highly correlated in both sexes (women r2 = 0.97, p < 0.001, men r2 = 0.91, p < 0.001), although the regression line for men was significantly different from the line of identity (p = 0.043). These results suggest modest trends toward underestimation of FMDXA in men when FMIVNA < 18 kg, and overestimation in men when FMIVNA > 18 kg. delta FM (IVNA-DXA) was not significantly related to any combination of skinfold thickness and circumferences in either gender. Age explained 27% of the variance in delta FM for the men (p = 0.008). Furthermore, delta FM was not significantly related to inter-method disparity in total-body bone mineral measurements in men or women (p < 0.05). The present study demonstrates strong correlation in fat measurements between IVNA and DXA in men and women ranging from normal to markedly obese. Correction for subject anthropometry does not significantly improve this relationship.

Absorptiometry, Photon↗
PubMed1997

Spinal somatosensory evoked potentials after epidural isoproterenol in awake sheep.

PURPOSE: The use of 10-15 micrograms epinephrine as an epidural test-dose is controversial. Isoproterenol would be a better alternative. However, before 5 micrograms isoproterenol can be incorporated in an epidural test-dose, neurotoxicological studies have to be performed. The present study was designed to assess spinal somatosensory evoked potentials (spinal SSEP) before and after epidural isoproteronol. METHODS: Spinal SSEPs were recorded before, 30 min after, and 72 hr after 50 micrograms isoproterenol were given epidurally (L3-4) to six chronically instrumented awake sheep. The spinal SSEPs after epidural (L3-4) administration of 15 ml lidocaine 2% were used to evaluate the model. The SSEPs were generated by transcutaneous stimulation of the sciatic nerve in the thigh. Spinal SSEPs were recorded directly from the spinal cord at vertebra T12 using a monopolar epidural electrode referenced to a subcutaneous needle electrode in the adjacent paraspinal area. RESULTS: Thirty minutes and 72 hr after epidural injection of 50 micrograms isoproterenol the latency and the amplitude of the SSEP waves were similar to baseline values. After lidocaine, no SSEPs could be generated in three sheep while in three sheep the latency of wave 2 (W2) was prolonged and the amplitude diminished. CONCLUSION: Administration of epidural isoproterenol did not affect spinal SSEPs in this study indicating an absence of neurotoxic side effects.

Adrenergic beta-Agonists↗
PubMed1997

[Obstetrical pain therapy].

Until today, the use of epidural analgesia in obstetrics still remains controversial. In the opinion of many obstetricians the use of an epidural for a healthy laboring parturient is not necessary and can lead to potentially harmful side effects. However, painful labor leads to a maternal stress reaction with the release of epinephrine and norepinephrine. The resulting vasoconstriction of uterine arteries can induce fetal asphyxia in an otherwise healthy fetus or can aggravate asphyxia in already compromised fetuses. Several studies show that epidural analgesia can attenuate the maternal stress reaction and thereby improve maternal and fetal well-being, as long as precautions are taken. The avoidance of maternal hypotension with sufficient volume preload with lactated Ringer's solution or colloids, and decreasing the concentration of local anaesthetics by adding opioids will prevent an increase in instrumental deliveries. With the use of patient-controlled epidural analgesia (PCEA) the amount of local anaesthetics can even further be reduced.

Analgesia, Epidural↗