Pharmacodynamics and pharmacokinetics of thiopental

Thiopental is an ultra short-acting barbiturate which remains the standard against which other induction agents are judged; it is also indicated for the therapy of brain hypoxic-ischaemia injuries and status epilepticus. Aspects of drug distribution that govern the onset and end of drug effect have been intensively studied to determine which parameters (in patient characteristics, diseases and administration modalities) influence effective dose and concentrations in individual patients. Thiopental has been used as a reference for pharmacokinetic and/or pharmacodynamic models in the study of rapid and short acting effect drugs. In anaesthesiology the pharmacokinetics of thiopental are described as linear; when doses and duration of treatment increase, nonlinear pharmacokinetics occur because of the saturation and/or the induction of the metabolism.     

Acute corticosteroid myopathy in intensive care patients

Several recent studies have attributed the occurrence of acute myopathy in intensive care unit patients to the combination of corticosteroids and neuromuscular junction blocking agents (NMBAs) used for mechanical ventilation. We present 4 patients who developed acute myopathy after administration of high doses of glucocorticoids during sedation with propofol without any NMBAs. All patients had elevated creatine kinase levels. Electrophysiological studies indicated normal motor and sensory nerve conduction velocities but reduced motor nerve response amplitudes. Needle electromyography identified abnormal spontaneous activity; motor unit potentials were polyphasic of low amplitude and short duration, characteristic of a myopathic process. Muscle biopsy demonstrated a prominent acute necrotizing myopathy in all 4 patients with a loss of thick filaments. Our observations support glucocorticoids rather than NMBAs as the main offending drug in acute corticosteroid myopathy. The predisposing factor should be the hypersensitivity of paralyzed muscles to corticosteroids regardless of the drug inducing paralysis: NMBAs or propofol.     

Clinical pharmacokinetics of cumulative very high dose of cisplatin in chemotherapy resistant solid tumors

The antagonist and agonist binding sites of muscarinic receptors were investigated by using membrane preparations of airways from nonsensitized normal control, sensitized control and repeatedly antigen challenged rats. The in vitro bronchial responsiveness to ACh was markedly increased in repeatedly antigen challenged group but not in sensitized control group. No significant difference was observed in receptor density and antagonist affinity among these three groups. The affinity of ACh for high-affinity agonist binding sites of repeatedly antigen challenged group was much greater than those in the other groups; the affinity significantly reduced in the presence of GTP gamma S. We concluded that enhanced G protein level might be involved in inducing airway hyperresponsiveness in rats.     

Radiology in the neonatal intensive care unit: dose reduction and image quality

This paper describes a prospective study of the diagnostic radiation doses received in a neonatal intensive care unit (NICU) for a representative radiological technique used at our institution for a number of years and a "low dose" technique similar to that recommended by the Commission of the European Communities (CEC). A 400 speed film-screen combination was used in both techniques. A total of 363 anteroposterior (AP) chest and abdominal films of 77 neonates were accrued. For each radiograph, the entrance skin dose (FSD), energy imparted (EI) and mean whole body dose were determined. For a neonatal AP chest, there was an 18% reduction in the mean ESD per radiograph from 20.0 muGy for the representative technique to 16.4 muGy for the low dose technique (p < 0.0005). The reduction in the mean EI per radiograph values for the two techniques from 7.9 muJ to 7.1 muJ (10%) was statistically significant at the p < 0.017 level, after compensating for the difference in mean field dimensions between the two patient cohorts. The mean whole body dose per radiograph reduction from 4.4 to 3.5 muGy (20%) was statistically significant at the p < 0.0028 level. It was determined that the ESD and EI could be fitted by an exponential function in the equivalent patient diameter, a single parameter indicative of neonate size. Absolute excess childhood cancer mortality risk per film was estimated using risk factors derived for fetal exposures. A "worst case" absolute excess mortality risk per chest radiograph was estimated to be 1.40 x 10(-7) for the conventional technique and was further reduced to 1.11 x 10(-7) for the low dose technique. A blind comparison of patient-matched film pairs for each technique was performed by three radiologists using criteria similar to those specified by the CEC. No statistically significant difference in clinical image quality was found between the two techniques.     

Factors causing stress in patients in intensive care units

Intensive care units have been considered stress generating areas. Knowing the causes why this happens will allow us to take specific measures to prevent or minimize it. This study has been performed with the aim to identify stress raising factors, as they are perceived by intensive care patients. The study has been performed in 49 patients most of whom were being attended in postoperatory control. The valuation of the degree of stress was performed using the "Scale of Environmental Stressors in Intensive Care" by Ballard in 1981, modified and adapted to our environment, with a result of 43 items distributed in six groups; Immobilization, Isolation, Deprivation of sleep, Time-spacial disorientation, Sensorial deprivation and overestimulation, and depersonalization and loss of autocontrol. The level of stress perceived by patients was low. The factors considered as most stressing were those related to physical aspects; presence of tubes in nose and mouth, impossibility to sleep and presence of noise, whereas those less stressing referred to Nursing attention. We conclude that patients perceive ICU as a little stressing place in spite of the excessive noise, remark the presence of invasive tubes and the difficulty to sleep as the most stressing factors, and in the same way, express a high degree of satisfaction about the attention received.     

Single dose pharmacokinetics of manidipine in hepatic impaired patients and healthy controls

The pharmacokinetics and safety of a single oral dose of 20 mg manidipine dihydrochloride have been studied in 8 patients with mild to moderate hepatic impairment (grade A or B in Child's classification, or score < or = 7 in Pugh's modification of Child's classification), and in 12 healthy subjects. They received one 20 mg manidipine dihydrochloride tablet with 100 ml of tap water after a standard breakfast. Manidipine was determined using HPLC with electrochemical detection from plasma samples taken up to 24 or 36 h after dosing. The medication was well tolerated. A trend toward higher Cmax, AUC, and MRT was observed in patients with a more severe hepatic impairment, as a consequence of reduction in the liver metabolic function. Patients with grade A hepatic impairment did not exhibit significantly altered pharmacokinetics with respect to healthy subjects, while grade B impairment patients had significantly higher AUC and MRT. Tmax values pointed to reduced absorption rate in patients compared to healthy subjects; the changes were more evident in grade B than grade A patients, although statistical significance was not reached. The reduction in absorption rate in grade B patients is probably related to their higher mean age, since this effect has been reported for manidipine. The pharmacokinetics of manidipine seem only modified in patients with a certain degree of hepatic impairment (at least Pugh grade 6 and Child grade B); therefore, adaptation of the dosing regimen does not seem to be generally recommendable, but should be modulated according to the liver status of the patient.     

Strategy for intensive care in patients with subarachnoid hemorrhage

Severe medical complications account for 20-30% of all deaths in patients with subarachnoid hemorrhage. High quality of intensive care is needed to prevent and correct pulmonary complications and electrolyte disturbances. Guidelines of intensive medical treatment should be defined to control intracranial hypertension and ischemic secondary cerebral damage in comatose patients. Extensive monitoring is necessary to achieve adequate observation in the perioperative period and safe treatment of vasospasm. A multidisciplinary approach in a critical area with intensive and sub-intensive beds, based on the cooperative role of neurosurgeons and anesthetists/intensivists, could improve the medical care, reducing complications, ICU stay and costs.     

Medical liability in the treatment of intensive care unit patients

Critical care medicine was practiced informally during several years, specially during war periods. Nowadays it is, however, a fundamental part of health systems in which patients attain care facilities of increasing complexity in a cost effective manner, according to their needs. The importance of this discipline in Chile, during its 30 years of development, has progressively increased and at the present time, intensive care units represent up to 30% of the total number of beds in some hospitals. Even though these units require great budgets and many resources, their place and the role of physicians who work in them has not been recognized adequately by the national medical community. The present document presents the official position of the Chilean Society of Intensive Medicine on the general objectives of this discipline. It indicates the scope of action of the specialty and the role of intensive care physicians, their relationship with other specialties, their duties and responsibilities with their patients.     

Continuous "high flux" dialysis: an effective renal replacement therapy for intensive care patients

Currently available replacement therapies for the treatment of acute renal failure are reviewed. Particular interest is focused on their application in intensive care, especially in septic patients. Underlying principles and mechanisms of action are explained. The continuous "High flux-dialysis" is shown to be a particularly effective form of renal replacement therapy.     

Awakening of intensive care patients after prolonged continuous sedation

OBJECTIVE: To investigate the relevance of the Symptom Checklist 90-R Obsessive-Compulsive subscale to cognition in individuals with brain tumor. DESIGN: A prospective study of patients assessed with a neuropsychological test battery. SETTING: A university medical center. PATIENTS: Nineteen adults with biopsy-confirmed diagnoses of malignant brain tumors were assessed prior to aggressive chemotherapy. MAIN OUTCOME MEASURES: Included in the assessment were the Mattis Dementia Rating Scale, California Verbal Learning Test, Trail Making Test B, Symptom Checklist 90-R, Mood Assessment Scale, Beck Anxiety Inventory, and Chronic Illness Problem Inventory. RESULTS: The SCL 90-R Obsessive-Compulsive subscale was not related to objective measures of attention, verbal memory, or age. It was related significantly to symptoms of depression (r = .81, P < .005), anxiety (r = .66, P < .005), and subjective complaints of memory problems (r = .75, P < .005). Multivariate analyses indicated that reported symptoms of depression contributed 66% of the variance in predicting SCL 90-R Obsessive-Compulsive Scores, whereas symptoms of anxiety contributed an additional 6% (P < .0001). CONCLUSIONS: Our data suggest that the SCL 90-R is best viewed as an indicator of unidimensional emotional distress and somatic effects of structural brain injury.     

Ward versus intensive care management of high-risk surgical patients

BACKGROUND: Selection of high-risk surgical patients for preoperative and perioperative admission to an intensive therapy unit (ITU) for enhancement of oxygen delivery may reduce postoperative morbidity and mortality rates. Limited resources may prevent admission of all suitable patients. This audit study examined whether it is possible to select patients most at risk and thus reduce surgical morbidity and mortality rates when ITU services are limited. METHODS: This was a retrospective audit comparing the actual outcomes of complications and death with predicted outcomes using the POSSUM score (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) for 101 general surgical and vascular patients who would have fulfilled previously suggested criteria for preoperative admission to the ITU. Main outcome measures were the number of preoperative ITU admission criteria, American Society of Anesthesiologists (ASA) and POSSUM scores, preoperative oxygen delivery values, intravenous fluid therapy, length of ITU stay, length of hospital stay, postoperative complications and 28-day mortality. RESULTS: Medical staff allocated patients appropriately. There was a lower mortality rate than predicted from individual POSSUM scores. Patients who were admitted to the ITU before operation had the highest ASA scores, admission criteria and POSSUM scores; they also had significantly lower mortality and morbidity rates than predicted by the POSSUM scoring system. CONCLUSION: Patients with the greatest reduction in mortality and morbidity rates were admitted to the ITU before operation and had cardiovascular physiology 'optimized' before surgery.     

Antibacterial therapy in pyo-sepsis complications of patients in intensive care units

A combined psychophysiologic study of 100 individuals living in territories contaminated by radionuclides and 60 people from ecologically clean region. There were no significant differences in the incidence of neurotic disorders between people from these regions (61.2 and 65.3%, respectively). The highest sensitivity to small radiation doses was observed at rather young age (20-40 years). It was found that a considerable role in the development of borderline psychic disorders belongs to both somatic disturbances due to low-dose radiation and psychogenic effects. A combined action of psychogenic and somatogenic factors aggravated symptoms of neurotic disorders and promoted widening of a range of psychic disturbances. Some part of the population from the contaminated territories tended to the development of cerebro-vascular psychoorganic pathology resultant from a breakdown of the reserves of the adaptation. Now the stress factor of radionuclides exposure is not so important as social and economic problems.     

Quality of care in intensive care units. Retrospective study on long-term patients]

Nursing care must be evaluated in order to determine its effectiveness and identify deficiencies, which makes it possible to introduce corrective measures to optimize quality. The quality of care given to patients in our unit was evaluated with a retrospective analysis of 915 records in the Nursing Care Plan corresponding to 59 patients with a mean ICU stay of 15.5 days. Six areas of care and indicators of deficient practice were identified: orotracheal intubation: accidental disconnection, displacement, obstruction, and pressure sores on lips; arterial catheterization: accidental disconnection and obstruction; central venous catheterization: accidental disconnection and contamination; urinary catheterization: accidental disconnection and urinary bacteriology; nasogastric intubation: accidental disconnection, obstruction, and nasal pressure sores; conservation of skin integrity: presence of pressure sores, and prevention of falls from the bed or chair. The reference standards were taken from the published literature. The results show that airway care was adequate, although the frequency of pressure sores on the lip produced by orotracheal tubes was high. The indicators for following up the care of vascular and urinary catheters showed results similar to established standards. There was a high rate of nasogastric tube obstruction due to the administration of medication. Finally, the frequency of pressure sores was well below established standards and there were no accidental falls. It is concluded that the detection of areas in which care is deficient requires an analysis of relevant nursing activities so that corrective measures can be taken. This study is a useful baseline for future quality control.     

False-positive LSD testing in urine samples from intensive care patients

Unexpected positive results for lysergic acid diethylamide (LSD) were found in urine samples from 12 patients in an intensive care unit in a routine screening using the CEDIA DAU assay. None of these test results could be confirmed by high-performance liquid chromatography analysis, but all samples contained the mucolytic drug ambroxol. Further studies demonstrated that ambroxol exhibits a significant cross-reactivity in the CEDIA DAU LSD assay. Therefore, positive LSD results obtained with the CEDIA DAU assay have to be critically evaluated, particularly during the cold season, when infections of the respiratory tract often result in more frequent use of mucolytic medications.