ABSTRACT
Poliomyelitis remains endemic in many developing nations. Patients may develop residual muscle weakness in one or more limbs after an attack of poliomyelitis in childhood. We report an adult patient who presented for right temporal cortical grid placement. He had childhood poliomyelitis and, while showing no evidence of postpolio syndrome, demonstrated excessive sensitivity to nondepolarizing muscle relaxants and developed prolonged muscle weakness during the postoperative period.
Subject(s)
Anesthesia , Craniotomy , Muscle Weakness/chemically induced , Neuromuscular Nondepolarizing Agents/adverse effects , Pancuronium/adverse effects , Poliomyelitis/complications , Postoperative Complications/chemically induced , Critical Care , Humans , Male , Middle Aged , Preanesthetic MedicationABSTRACT
We Japanese anesthesiologists can now use rocuronium as well as vecuronium. Although the onset of rocuronium is more rapid, the non-depolarizing neuromuscular blocking (NMB) agent has similar characteristics of duration and recovery compared to vecuronium. Reversal of NMB is therefore essential to recover patients safely. Conventional standard of reversal of NMB [train of four (TOF) >0.7] is not enough to have sufficient vital capacity and inspiratory force, resulting in pulmonary regurgitation or atelectasis. Even though the reversal of NMB cannot sufficiently be completed by anti-cholinesterase (ChE) agents such as neostigmine, it is needed to reverse the NMB because of their late spontaneous recovery. We also have to take care of patients with neuromusclar diseases such as Duchenne-type muscle dystrophy, when we use anti-ChE agents. Sugammadex is a novel and unique compound designed as an antagonist of rocuronium and possibly other steroid NMB agents. Sugammadex exerts its effect by forming very tight water-soluble complexes at a 1 : 1 ratio with steroid NMB agents (rocuronium>vecuronium>>pancuronium). PhaseIII trials in Japan as well as Europe and the US have just been finished, and it is expected to be used clinically in the near future.
Subject(s)
Cholinesterase Inhibitors/pharmacology , Neostigmine/pharmacology , Neuromuscular Blocking Agents/adverse effects , Neuromuscular Blocking Agents/antagonists & inhibitors , Androstanols/adverse effects , Androstanols/antagonists & inhibitors , Anesthesia Recovery Period , Cholinesterase Inhibitors/administration & dosage , Clinical Trials, Phase III as Topic , Humans , Neostigmine/administration & dosage , Neuromuscular Diseases , Pancuronium/adverse effects , Pancuronium/antagonists & inhibitors , Rocuronium , Sugammadex , Vecuronium Bromide/adverse effects , Vecuronium Bromide/antagonists & inhibitors , gamma-Cyclodextrins/administration & dosage , gamma-Cyclodextrins/pharmacologyABSTRACT
Neuromuscular-blocking agents are commonly used in laboratory animal research settings. Due to actions of cholinergic receptors at locations other than the motor end-plate, these agents have a strong propensity to modulate autonomic outflow and may therefore not be desirable in studies examining autonomic function. This study aimed to compare the effect of two non-depolarizing neuromuscular-blocking agents, pancuronium and cisatracurium, on blood pressure, heart rate and non-invasive indices of autonomic function (heart rate variability, systolic blood pressure variability and baroreflex sensitivity) under two different types of anaesthesia in Lewis rats. Pancuronium produced a profound vagolytic response characterized by tachycardia, reduction in heart rate variability and baroreflex sensitivity under urethane anaesthesia, and with minimal effect under isoflurane anaesthesia. Conversely, cisatracurium produced no evidence of vagolytic action under either urethane or isoflurane anaesthesia. Therefore, for studies interested in examining autonomic function, particularly baroreflex or vagal function, neuromuscular blockade would be best achieved using cisatracurium.
Subject(s)
Anesthetics/adverse effects , Baroreflex/drug effects , Blood Pressure/drug effects , Heart Rate/drug effects , Neuromuscular Blocking Agents/adverse effects , Rats/physiology , Animals , Atracurium/adverse effects , Atracurium/analogs & derivatives , Female , Isoflurane/adverse effects , Male , Pancuronium/adverse effects , Rats, Inbred Lew , Urethane/adverse effectsABSTRACT
We report acute complete external ophthalmoplegia and severe myopathy in a patient treated with high doses of IV methylprednisolone and pancuronium. Awareness of this rare syndrome in a common clinical setting can lead to prompt recognition and avoid confusion with other causes of acute weakness and ophthalmoparesis.
Subject(s)
Methylprednisolone/adverse effects , Muscular Diseases/chemically induced , Ophthalmoplegia/chemically induced , Pancuronium/adverse effects , Acute Disease , Humans , Male , Methylprednisolone/therapeutic use , Middle Aged , Pancuronium/therapeutic useABSTRACT
Pancuronium bromide (Pavulon) is used to induce skeletal muscle paralysis in preterm infants, presumably for effective ventilatory support during acute respiratory failure. Twelve infants with respiratory failure were evaluated for sequential changes in pulmonary mechanics during continuous pancuronium administration (0.1 mg/kg every two to three hours) for more than 48 hours. The study weight of the neonates ranged from 980 to 2,950 g, and the postconceptional age ranged from 27 to 41 weeks. Pulmonary compliance, resistance, and resistive work of breathing were determined, using least mean square analysis technique, daily for three days and after discontinuation of pancuronium (even though there was no clinical improvement in ventilatory management). The dynamic pulmonary compliance decreased from 0.38 +/- 0.05 to 0.30 +/- 0.04 mL/cm H2O/kg (mean +/- SE) (P less than .05) and the total pulmonary resistance increased 51% from 115.6 +/- 21.3 to 174.9 +/- 27.3 cm H2O/L/s (P less than .005) during prolonged skeletal muscle paralysis. Upon discontinuation of pancuronium, the dynamic pulmonary compliance increased 43% to 0.43 +/- 0.4 mL/cm H2O/kg (P less than .05) and the total pulmonary resistance decreased by 41% (P less than .005). These data question the advisability of prolonged skeletal muscle paralysis in neonates and suggest the need for further detailed evaluation of the effects of prolonged paralysis on neonatal pulmonary mechanics.
Subject(s)
Lung/drug effects , Pancuronium/adverse effects , Paralysis/chemically induced , Humans , Infant , Infant, Newborn , Pancuronium/therapeutic use , Respiratory Distress Syndrome, Newborn/drug therapy , Respiratory Function TestsABSTRACT
BACKGROUND: Acute myopathy following mechanical ventilation for near-fatal asthma (NFA) has been described recently, and some researchers have suggested that this complication is related to the use of neuromuscular blocking agents (NMBAs) and corticosteroids (CSs). OBJECTIVES: To determine the incidence of acute myopathy in a group of patients and to examine the most important predictors of its development. DESIGN AND METHODS: A retrospective cohort study over a 10-year period (1985 to 1995) of all asthma patients who received mechanical ventilation at two centers in Vancouver (designated center 1 and center 2). RESULTS: In center 1, there were 58 patients who had 64 episodes of NFA, and in center 2, there were 28 patients who had 30 episodes. NMBAs were used in 30 of 86 admissions for acute severe asthma (35%). The mean (+/- SD) duration of muscle paralysis was 3.1+/-2.3 days. A total of 9 patients (10.4%) developed significant myopathy. The incidence of myopathy was 9 of 30 (30%) among patients who received NMBAs. In a multiple logistic regression model, the development of myopathy was only significantly associated with the duration of muscle relaxation. The odds ratio for the development of myopathy increased by 2.1 (95% confidence interval, 1.4 to 3.2) with each additional day of muscle relaxation. The dose and the type of the CS were not significantly associated with the myopathy in the multiple logistic regression analysis. CONCLUSION: Our study showed that there is a high incidence of acute myopathy when NMBAs are used for NFA. The incidence of myopathy increases with each additional day of muscle relaxation.
Subject(s)
Asthma/therapy , Glucocorticoids/adverse effects , Neuromuscular Blocking Agents/adverse effects , Neuromuscular Diseases/chemically induced , Respiration, Artificial/methods , APACHE , Acute Disease , Adult , Electromyography , Female , Follow-Up Studies , Humans , Hydrocortisone/adverse effects , Incidence , Male , Methylprednisolone/adverse effects , Middle Aged , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/epidemiology , Odds Ratio , Pancuronium/adverse effects , Retrospective StudiesABSTRACT
During six consecutive months, seven patients admitted to our ICU (15 beds, general ICU, approximately 300 intubated patients per year) for acute respiratory failure requiring intubation and mechanical ventilation presented with a peculiar neuromuscular disorder. After the occurrence of this cluster group of patients, we detected two more similar but isolated cases in the following 18 months, ie, altogether 9 patients in 2 years of observation, or 1.55 percent of all intubated patients in our ICU. Sedation was achieved using midazolam, curarization was effected with the neuromuscular non-depolarizing agent pancuronium bromide (PB), and corticosteroids were administered to eight patients. Shortly after discontinuation of sedation and curarization, we observed a persistent tetraparetic syndrome and/or peroneal palsy with a concomitant increase of serum creatine kinase (CK). None of the patients was septic or had the multisystem organ failure. A strong association between CK increase and PB administration was found, whereas no patient suffered severe liver or kidney failure. The duration of the neurologic deficit ranged from 4 to 52 weeks, with only partial recovery for some patients; the duration of dysfunction was apparently related to the total dose of corticosteroids received. Two patients had difficulty being weaned from the respirator and required tracheostomy. Electrophysiologic studies showed signs of axonal neuropathy and myopathic changes, ie, motor units of brief duration, small amplitude, overly abundant for the voluntary effort being exerted. Muscle biopsies showed significant myopathic alterations, with foci of muscle necrosis in most patients and minimal lymphocytic inflammation in one patient. The neurologic complication described differs from the polyneuropathy in critically ill patients. Furthermore, PB or corticosteroids or both appear to be the causal agents. The duration of the neuromuscular dysfunction may be related to concomitant steroid therapy. The CK enzyme seems to be a marker of the disorder. This disorder is associated with myopathic alterations and axonal degeneration in some patients. Pancuronium bromide should be used with caution, particularly when associated with steroids therapy, and it may cause difficulty in weaning patients from the respirator.
Subject(s)
Neuromuscular Diseases/chemically induced , Pancuronium/adverse effects , Respiration, Artificial , Adult , Aged , Cluster Analysis , Creatine Kinase/blood , Electromyography , Female , Humans , Intensive Care Units , Male , Middle Aged , Muscles/pathology , Neural Conduction , Neuromuscular Diseases/epidemiology , Neuromuscular Diseases/pathology , Neuromuscular Diseases/physiopathology , Paresis/chemically induced , Paresis/epidemiology , Paresis/pathology , Paresis/physiopathologyABSTRACT
General anesthetics may have diverse effects on intraocular pressure, possibly leading to serious complications such as vitreous loss and iris prolapse. Clinical and research findings on the effects of depolarizing and nondepolarizing agents are discussed, and methods of avoiding or counteracting adverse reactions are summarized.
Subject(s)
Anesthesia, General/adverse effects , Anesthetics/adverse effects , Intraocular Pressure/drug effects , Anesthesia, Inhalation/adverse effects , Anesthetics/pharmacology , Aqueous Humor/drug effects , Child , Gallamine Triethiodide/adverse effects , Gallamine Triethiodide/pharmacology , Humans , Ketamine , Muscle Relaxants, Central , Oculomotor Muscles/drug effects , Pancuronium/adverse effects , Pancuronium/pharmacology , Succinylcholine/adverse effects , Succinylcholine/pharmacology , Tubocurarine/adverse effects , Tubocurarine/pharmacologyABSTRACT
We cared for a 4-year-old patient who had undergone orthotopic liver transplantation and was placed on a ventilator for respiratory distress associated with Pneumocystis carinii pneumonia. The neuromuscular blocking agent pancuronium bromide 1.0-1.2 mg every hour as needed was used to facilitate artificial ventilation for 40 days. On discontinuation of pancuronium, the patient experienced severe, generalized neuromuscular dysfunction. Because no improvement was seen for 2 weeks, the acetylcholinesterase inhibitors edrophonium and pyridostigmine were instituted. Shortly thereafter the patient's condition began to improve. Gradual improvement occurred over 3-4 months and the patient has since returned to baseline neurologic function. We suggest that long-term pancuronium use was the cause of the patient's prolonged paralysis. The improvement experienced after the initiation of antidotal therapy strongly supports our proposal.
Subject(s)
Liver Transplantation , Pancuronium/adverse effects , Paralysis/chemically induced , Child, Preschool , Cholinesterase Inhibitors/therapeutic use , Female , Humans , Paralysis/drug therapy , Paralysis/physiopathologyABSTRACT
Recent literature suggests that the risk of prolonged neuromuscular blockade associated with atracurium compared with other nondepolarizing neuromuscular blocking agents may be minimal. Two patients experienced prolonged weakness associated with the administration of atracurium. Both received atracurium 0.5-0.7 mg/kg/hour in combination with methylprednisolone 500-600 mg/day. Electromyographic results and creatine kinase levels were suggestive of muscular weakness in both patients. Despite high-dose corticosteroid therapy, the electromyographic evidence supporting prolonged weakness did not suggest typical corticosteroid myopathy. Although some clinicians advocate routine administration of atracurium in critically ill patients due to the relative lack of reports of prolonged weakness, this may be premature. Although there are fewer reports of atracurium-associated prolonged weakness compared with pancuronium and vecuronium, the patients we describe suggest that it may occur.
Subject(s)
Atracurium/adverse effects , Neuromuscular Junction/drug effects , Aged , Asthma/complications , Atracurium/pharmacology , Creatine Kinase/blood , Electromyography , Female , Humans , Hypertension/complications , Intubation, Intratracheal , Methylprednisolone/administration & dosage , Middle Aged , Muscle Hypotonia/chemically induced , Pancuronium/adverse effects , Pancuronium/pharmacology , Vecuronium Bromide/adverse effects , Vecuronium Bromide/pharmacologyABSTRACT
Nondepolarizing neuromuscular blocking agents (NNMBAs) are frequently administered to patients in the intensive care unit (ICU). We conducted a retrospective study of patients in intensive care who received infusions (> 48 hrs) of commonly used NNMBAs. The goals were to describe NNMBA use in our ICUs, determine patient characteristics, and assess the cost of the individual drugs. We found that atracurium was prescribed for 68% of study patients; 68% of the patients did not have renal, hepatic, or cardiovascular disease; dosages of NNMBAs varied; a statistically significant increase in dosage requirements over time occurred with atracurium; assessment of neuromuscular blockade was 100% subjective; and 41% and 17% of patients receiving atracurium and vecuronium, respectively, experienced prolonged neuromuscular weakness documented subjectively. As a result of this study, guidelines for agent selection were developed to facilitate cost effective use of NNMBA in our ICUs. Using these guidelines would potentially significantly decrease drug expenditures in this setting.
Subject(s)
Neuromuscular Nondepolarizing Agents/therapeutic use , Adult , Aged , Aged, 80 and over , Atracurium/adverse effects , Atracurium/economics , Atracurium/therapeutic use , Child, Preschool , Cost Savings , Drug Costs , Drug Utilization Review , Female , Hospital Bed Capacity, 300 to 499 , Humans , Infusions, Intravenous , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Minnesota , Pancuronium/adverse effects , Pancuronium/economics , Pancuronium/therapeutic use , Retrospective Studies , Time Factors , Vecuronium Bromide/adverse effects , Vecuronium Bromide/economics , Vecuronium Bromide/therapeutic useABSTRACT
Severe hypertension, tachycardia or ECG changes have been reported following i.v. administration of pancuronium to patients with pheochromocytoma or bronchial asthma. These cardiovascular changes were explained by an interaction between autonomic effects of pancuronium and elevated serum catecholamines or aminophylline. We noted similar cardiovascular changes associated with i.v. administration of pancuronium in two patients after successful cardiopulmonary resuscitation and in two with midbrain hemorrhage and epidural hematoma. In these patients, pancuronium produced no abnormal cardiovascular changes when given during elective surgery or before the occurrence of midbrain hemorrhage. Thus, ischemic brain damage may play a role in producing the severe cardiovascular changes associated with pancuronium.
Subject(s)
Brain Injuries/complications , Hypertension/etiology , Pancuronium/adverse effects , Resuscitation , Tachycardia/etiology , Aged , Electrocardiography , Female , Humans , Male , Middle AgedABSTRACT
A comparative study of two low-dose oral contraceptives, gestodene (GES) 75 mcg/ethinyl oestradiol (EE) 30 mcg and desogestrel (DES) 150 mcg/EE 20 mcg, was conducted in women over 30 years of age. This randomised, open-label study was organised in Denmark, Italy, New Zealand and United Kingdom. A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles. The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline. However, the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment. The mean age (+/- SD) was 35 +/- 4 years in the GES/EE group and 35 +/- 5 years in the DES/EE group. The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group, data for 2796 cycles. There were no pregnancies on medication with either preparation. The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6. Irregular bleeding between withdrawal bleeds occurred in 10% of GES/EE and 18.5% of DES/EE cycles. Absence of all bleeding was reported in 29 (1%) and 63 (2%) cycles, respectively. The incidence of missed pills was low in both groups (11% of cycles). No significant differences were observed in cycle length or withdrawal bleeding episode length. Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE. However, for both preparations, the mean intensity was close to light bleeding. No clinically significant differences were noted in weight, blood pressure, Papanicolaou smears or laboratory data. Sixty-eight (13.5%) subjects in the GES/EE group and 64 (12.8%) in the DES/EE group discontinued before the end of the study. Among them, 37 (7%) and 40 (8%) in the respective groups withdrew because of adverse reactions. There was no difference between groups in terms of primary reasons for withdrawal. The most frequently reported complaints that led to discontinuation in both groups were headache, nausea and metrorrhagia. Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group. These results show excellent cycle control, efficacy and very low rate of side effects with both GES/EE and DES/EE. These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause.
PIP: At 66 sites in Denmark, Italy, New Zealand, and the UK, clinicians randomly allocated 1006 women 30 years old, some of whom were in their early 50s, into 1 of 2 groups receiving a low-dose oral contraceptive (OC): Minulet containing 75 mcg gestodene (GES)/30 mcg ethinyl estradiol (EE) and Mercilon containing 150 mcg desogestrel (DES)/20 mcg EE. The study aimed to compare these 2 low-dose OCs to help physicians prescribe an OC that could be continued into later years. Before treatment, the 2 groups had similar demographic and gynecologic characteristics. The mean menstrual flow length in the GES/EE group was longer than that of the DES/EE group (4.7 days vs. 4.5 days; p = .035) though. None of the women during 2800 cycles of GES/EE use and 2796 cycles of DES/EE use conceived, even though women forgot to take at least 1 pill in 11% of cycles. The GES/EE OC had significantly better cycle control than did the DES/EE OC. For example, the GES/EE group was more likely to have normal cycles than the DES/EE group (84-93% vs. 73-83%; p .001). The DES/EE group experienced a significantly lower withdrawal bleeding mean intensity than the GES/EE group in all 6 cycles, but the bleeding for both groups was close to light bleeding. The 2 groups were similar in weight, blood pressure, Papanicolaou smears, and laboratory data. Discontinuation rates for the GES/EE and DES/EE groups were 13.5% and 12.8%, respectively. Adverse reactions accounted for discontinuation in 7% of the GES/EE group and 8% of the DES/EE group. The major complaints leading to discontinuation were headache, nausea, and breakthrough bleeding. Both GES/EE and DES/EE had very good cycle control and efficacy and a very low rate of side effects. These results suggest that both these low-dose OCs would be acceptable for healthy nonsmoking women needing contraception up to menopause.
Subject(s)
Ethinyl Estradiol/administration & dosage , Norpregnenes/administration & dosage , Pancuronium/analogs & derivatives , Adult , Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Combined/adverse effects , Denmark , Ethinyl Estradiol/adverse effects , Female , Humans , Italy , Middle Aged , New Zealand , Norpregnenes/adverse effects , Pancuronium/administration & dosage , Pancuronium/adverse effects , United KingdomABSTRACT
The performance of a new low-dose oral contraceptive (Mercilon) containing only 20 micrograms ethinyloestradiol combined with 150 micrograms desogestrel is reviewed. Eight multicentre clinical trials have been completed and provide information on 10,672 women studied over 73,477 cycles. The high efficacy of Mercilon was indicated by the finding that only 10 pregnancies were reported; nine of these occurred in women who omitted to take Mercilon on a number of days and only one in a woman who took all the tablets according to instructions. Cycle control was good; as with all oral contraceptives, the incidence of breakthrough bleeding and spotting was highest in the first treatment cycle and by the sixth treatment cycle the values were usually < 5% and < 7%. More than 80% of women had regular cycles. Side effects were few, the most common being headache, nausea and breast tenderness with incidences in the sixth treatment cycle of less than 2%, 6% and 6%, respectively. There were no significant changes in body weight or blood pressure. Pharmacodynamic investigations showed no adverse effects. Only 1 of 5 studies found an increased response to a glucose tolerance test compared to the pretreatment test. In 8 of 10 studies, serum HDL-C concentrations increased on treatment and this was associated with increases in apoproteins A1 and A2. Serum triglyceride levels also increased but no change occurred in serum cholesterol or LDL-C levels. Haematological factors were assessed in 8 studies and only minor changes were observed. Serum binding protein (SHBG, CBG, caeruloplasmin) concentrations increased and serum androgen levels decreased. Measurements of blood FSH, LH, oestradiol and progesterone indicated adequate inhibition of ovulation. Mercilon is the only oral contraceptive containing 20 micrograms ethinyloestradiol to have high efficacy, to have no adverse pharmacodynamic effects and, importantly, to produce an acceptable bleeding pattern not significantly different from that of oral contraceptives with a higher content of ethinyloestradiol.
Subject(s)
Pancuronium/analogs & derivatives , Adult , Blood Proteins/analysis , Carbohydrate Metabolism , Clinical Trials as Topic , Female , Humans , Lipid Metabolism , Ovary/drug effects , Pancuronium/adverse effects , Pancuronium/pharmacology , Pituitary Gland/drug effectsABSTRACT
The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest, Femodeen, Marvelon, or Mercilon. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5 alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17 alpha-hydroxyprogesterone (170HP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon (-75%) as compared to the others (-100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.
PIP: Health researchers randomly assigned 100 healthy women aged 18-38 from the Netherlands and Saudi Arabia to one of four various oral contraceptive (OC) groups to undergo six cycles of OC therapy so they could evaluate changes in plasma concentrations of sex hormone binding globulin (SHBG), corticosteroid-binding globulin (CBG), albumin (Alb), testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), androstenedione (A), dehydro-epiandrosterone-sulphate (DHEA-S), and 17 alpha-hydroxyprogesterone (17OHP). The four monophasic OCs were Cilest (35 mcg ethinyl estradiol [E2] and 250 mcg norgestimate), Femodeen (30 mcg E2 and 75 mcg gestodene), Marvelon (30 mcg E2 and 150 mcg desogestrel), and Mercilon (20 mcg E2 and 150 mcg desogestrel). There were 12 dropouts. Neither body weight nor blood pressure changed significantly during the study. All steroidal serum parameters (T, FT, DHT, A, DHEA-S, 17OHP, Alb) fell significantly during the six cycles of OC treatment (ratio of decrease, 1.3-3), regardless of OC type. These changes had appeared after cycle 4. The only significant difference between the OC groups was that the mean decrease of DHEA-S for Mercilon was lower than that for the other OC groups (21% vs. 43% for Cilest, 44% for Marvelon, and 34% for Femodeen; p 0.05). SHBG and CBG rose greatly during OC use in all four OC groups (mean increase = 263% and 94%, respectively; p 0.05). The increase in CBG was significantly less in the Mercilon group than in the other OC groups (74% vs. 96% for Cilest, 101% for Femodeen, and 102% for Marvelon; p 0.05). These findings show that OC use changed the endogenous androgen environment in the direction of hypoandrogenism. Thus, all four OCs can equally treat androgen-related syndromes (e.g., acne and hirsutism).
Subject(s)
Androgens/blood , Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Combined/adverse effects , Ethinyl Estradiol-Norgestrel Combination/analogs & derivatives , 17-alpha-Hydroxyprogesterone , Adolescent , Adult , Androstenedione/blood , Dehydroepiandrosterone/analogs & derivatives , Dehydroepiandrosterone/blood , Dehydroepiandrosterone Sulfate , Desogestrel/administration & dosage , Desogestrel/adverse effects , Dihydrotestosterone/blood , Drug Combinations , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/adverse effects , Female , Humans , Hydroxyprogesterones/blood , Luteal Phase , Norgestrel/administration & dosage , Norgestrel/adverse effects , Norgestrel/analogs & derivatives , Norpregnenes/administration & dosage , Norpregnenes/adverse effects , Pancuronium/administration & dosage , Pancuronium/adverse effects , Pancuronium/analogs & derivatives , Progestins/administration & dosage , Progestins/adverse effects , Sex Hormone-Binding Globulin/metabolism , Testosterone/blood , Transcortin/metabolismABSTRACT
We present 3 patients with chronic renal failure who had postoperative paralysis due to the administration muscle relaxants. One of them received gallamine, a non-depolarizing blocking agent that is mainly excreted by the kidney (70--90%). Two of them received pancuronium bromide, also a non-depolarizing blocking agent which is partially excreted by the kidneys (37--44%). All of them received succinylcholine. Succinylcholine is hydrolyzed by the serum cholinesterase into succinylmonocholine and choline. These active metabolites are excreted by the kidney. These patients serve as examples of the importance of considering the route of excretion of drugs and their metabolites in clinical situations involving the renal failure patient. The pharmacology of drugs administered relative to surgical procedures is reviewed.
Subject(s)
Anesthesia/adverse effects , Kidney Failure, Chronic/complications , Neuromuscular Blocking Agents/adverse effects , Paralysis/chemically induced , Adult , Arteriovenous Shunt, Surgical , Female , Humans , Kidney/metabolism , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/surgery , Kidney Transplantation , Middle Aged , Pancuronium/adverse effects , Pancuronium/metabolism , Succinylcholine/adverse effects , Succinylcholine/metabolism , Transplantation, HomologousABSTRACT
The effect of pancuronium administration on catecholamine levels and blood pressure was investigated. Noradrenaline levels prior to paralysis amongst infants fighting the ventilator were high, but were significantly reduced following treatment with pancuronium. There was no significant change in either blood pressure or adrenaline levels. Increasing peak inspiratory pressure (approx. 4 cmH2O) immediately prior to paralysis effectively prevented the hypoventilation previously associated with the administration of the first dose of pancuronium.
Subject(s)
Blood Pressure/drug effects , Catecholamines/blood , Pancuronium/adverse effects , Paralysis , Epinephrine/blood , Female , Humans , Infant, Newborn , Infant, Premature , Male , Norepinephrine/blood , Respiration, ArtificialABSTRACT
This paper reports on 12 patients in a 3-year period (from 1st July 1980 to 1st July 1983) who were treated with artificial ventilation and with the muscle relaxant pancuronium bromide (Pavulon), over a period of 6 days or longer. After discontinuation of this drug these patients developed severe tetraparesis with areflexia, sometimes combined with disturbances of the extraocular and facial muscles and diffuse muscular atrophy, without sensory disturbances. Seven patients recovered completely after 2-5 months, two made an incomplete recovery and three died due to the primary disease. It is suggested that these neuromuscular complications were caused by prolonged high-dosage Pavulon treatment in combination with renal and hepatic disturbances and/or the use of aminoglucosides.
Subject(s)
Neuromuscular Diseases/chemically induced , Pancuronium/adverse effects , Respiration, Artificial , Adult , Aged , Electromyography , Humans , Middle Aged , Muscles/pathology , Muscular Atrophy/pathology , Nerve Fibers, Myelinated/pathology , Neuromuscular Diseases/pathology , Neuromuscular Diseases/physiopathology , Pancuronium/therapeutic useABSTRACT
The objective of this prospective double-blind study was to determine whether postoperative residual paralysis (PORP) after pancuronium or vecuronium results in hypoxemia and hypercapnia in the immediate admission period to the recovery ward. Eighty-three consecutive surgical patients received balanced or intravenous anesthesia with pancuronium for operations lasting longer than one hour or vecuronium for those lasting less than 60 min, both combined with neostigmine at the end of anesthesia. Standard clinical criteria assessed neuromuscular function intraoperatively. Postoperatively, we determined neuromuscular function (acceleromyography with supramaximal train-of-four (TOF) stimulation of the ulnar nerve, and a 5-s head lift) and pulmonary function (pulse oximetry: SpO2, and blood gas analysis: SaO2, PaCO2). We defined PORP as a TOF-ratio <70%, hypoxemia as a postoperative SpO2 > or =5% below the pre-anesthestic level together with a postoperative SaO2 <93%, and hypercapnia as a PaCO2 > or =46 mm Hg. Among the 49 pancuronium and 27 vecuronium patients studied, the PORP rates were 20% in the pancuronium group and 7% in the vecuronium group (p>0.05). Hypoxemia and hypercapnia occurred more often in pancuronium patients with PORP than in those without PORP namely 60% vs. 10% (p<0.05) and 30% vs. 8% (p>0.05), respectively. We conclude that PORP after pancuronium is a significant risk factor for hypoxemia.
Subject(s)
Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents/adverse effects , Pancuronium/adverse effects , Paralysis , Postoperative Complications , Vecuronium Bromide/adverse effects , Double-Blind Method , Humans , Paralysis/chemically induced , Postoperative Complications/chemically induced , Prospective Studies , RespirationABSTRACT
A female patient treated by mechanical ventilation with high doses of pancuronium and methylprednisolone for status asthmaticus presented with acute total areflexic and severe amyotrophic tetraplegia; she died after multiple organ failure. Muscle biopsy confirmed the clinical diagnosis of "acute corticosteroid myopathy", precipitated by a corticosteroid "disuse hypersensitivity" after pancuronium. The electromyogram showed a critical illness polyneuropathy, secondary to multiple organ failure. Nerve biopsy was normal. The respective parts played by corticosteroids, curare-like derivatives and intensive care in the genesis of unexplained difficulty in weaning from the ventilator are discussed.