A model to decrease hepatic blood flow and cardiac output with pressure breathing.

This randomized, controlled, crossover study evaluated the effect of continuous positive airway pressure (CPAP) breathing on hepatic blood flow (HBF) and cardiac output in 10 healthy male subjects. A CPAP mask was placed on the face and the subject breathed at either CPAP 12.5 cm H2O or ambient airway pressure. The estimated HBF was calculated as the ratio of indocyanine green plasma clearance to one minus the hematocrit. Cardiac output was measured with Doppler ultrasound. CPAP caused HBF to decrease in 8 of 10 subjects (14.1% +/- 15.3%, mean +/- SD, p = 0.033) and cardiac index (CI) to decrease in all subjects (14.1% +/- 5.7%, p = 0.0001). Stroke volume and respiratory rate were significantly decreased; heart rate was unchanged. These results indicate that CPAP at 12.5 cm H2O causes a small, but significant decrease in both HBF and CI.

Isoniazid-induced fever.

A 56-year-old man was started on therapy with isoniazid after exhibiting a positive reaction to an intradermal injection of intermediate-strength purified protein derivative of tuberculin. After the first dose and each of the following three doses, nausea, vomiting, chills, and an elevated body temperature ranging from 38 degrees C (100.4 degrees F) to 40 degrees C (104. degrees F) occurred. There was no evidence of a hypersensitivity reaction to isoniazid, such as cutaneous rash, eosinophilia, elevated concentration of IgE, and abnormal results on tests of hepatic function. Following discontinuance of therapy with isoniazid, the temperature returned to normal. This experience illustrates the potential of isoniazid to cause febrile reactions, a situation that could be misdiagnosed as an infectious process.

Influence of cardiopulmonary bypass on nitroglycerin clearance.

The effect of cardiopulmonary bypass on the clearance of nitroglycerin (NTG) was studied in seven patients scheduled for coronary artery bypass graft surgery. Intravenous NTG was administered through nonadsorbing tubing at a starting dosage of 5-10 micrograms/min and was adjusted as needed. Blood samples were obtained from the radial artery and antecubital vein before bypass and from the arterial outlet of the oxygenator during bypass at least 30 minutes apart during a constant dosage or at least 30 minutes after a dosage change. Serum concentrations were analyzed for NTG by gas chromatography. Venous NTG concentrations were always lower than concurrent arterial concentrations, with an average arteriovenous extraction of 67.2%. Serum concentrations of NTG were generally within the range associated with a therapeutic response in congestive heart failure patients. Consistent with other reports, NTG concentrations varied widely among patients and considerable intrasubject fluctuations in drug concentrations were seen. The mean +/- SD apparent clearance of NTG before bypass of 0.044 +/- 0.02 L/kg/min increased 20% to 0.052 +/- 0.02 L/kg/min during bypass (P = .05). These results suggest that cardiopulmonary bypass increases the clearance of NTG; however, the magnitude appears to be small and only partially explains the reported increased dosage needed during cardiopulmonary bypass.

Defining and achieving optimum therapeutic goals in critically ill patients.

Patients who are critically ill with sepsis, shock, respiratory failure, trauma, or major surgical procedures may have reduced morbidity and mortality when hemodynamic and oxygen transport variables are augmented to values higher than those traditionally considered normal. Lactate production and suboptimum oxygen transport values are associated with anaerobic metabolism and insufficient tissue oxygenation. Since lactate can be a marker of inadequate tissue oxygenation, serial lactate measurements may be useful in individualizing therapy to reverse tissue hypoxia. Optimum hemodynamic and oxygen transport values are highly individual, and no accepted method has been established for guiding therapy. These values, together with plasma lactate concentrations, may assist in individualizing therapy in critically ill patients. No consensus can be reached at this time as to which specific therapeutic end points are optimal, how to achieve these end points, and which subset of patients will benefit from this therapy.

Pharmacology and therapeutic use of low-dose dopamine.

The renal pharmacologic effects of intravenous dopamine in doses of 0.5-3.0 micrograms/kg/min include increases in renal blood flow, glomerular filtration rate, solute excretion, and urine flow. Clinical studies revealed that low-dose dopamine can reverse oliguria, but these studies were poorly controlled, were confounded by the use of other diuretics, had small patient populations, and often did not evaluate mortality or long-term renal function. When used in low doses, side effects are rarely seen. Because of dopamine's effect on hepatic and renal function, changes in drug clearance may occur. Low-dose dopamine may be considered in the early course of oliguric patients; however, specific advantages over other diuretic therapy have not been established.

Survey of ACCP members regarding use of computers and information processing.

A questionnaire was sent to a random sample of 480 members of the American College of Clinical Pharmacy to determine their opinions on various issues relating to computer technology and the future role of computers in information processing in pharmacy. Results from the 335 evaluable responses revealed nearly universal use of computers. Word processing was the most common application and IBM or compatible computers were the dominant machines. Respondents used a wide variety of generalized and specialized programs, especially electronic communication products. Computer technology is expected to have a major impact on routine aspects of pharmacy practice, although, respondents were split on its impact on more cognitively intensive functions.

Dobutamine: ten years later.

Dobutamine is a commonly used positive inotrope for the short-term management of heart failure. It is commercially available as a 50:50 mixture of two isomers with unique effects on alpha- and beta adrenergic receptors. In dosages of 2-15 micrograms/kg/minute, dobutamine has been shown to increase cardiac output (mainly through stroke volume), reduce systemic vascular resistance, lower central venous and pulmonary artery wedge pressures, improve renal blood flow, and relieve signs and symptoms of congestive heart failure. At higher dosages it can increase heart rate and induce arrhythmias. Recent evidence indicates that effects of dobutamine last long after the drug has been eliminated from the plasma, and some work has been done on ambulatory use of this agent. Dobutamine has been used successfully in several circumstances, such as after cardiac surgery, in patients with myocardial infarction, and in various shock states. An understanding of the pathophysiology of the underlying disorder is important in deciding which catecholamine to use. With this in mind, monotherapy or combination therapy with inodilators such as dobutamine, or inopressors like dopamine will follow logically.

Application of artificial intelligence to pharmacy and medicine.

Artificial intelligence (AI) is a branch of computer science dealing with solving problems using symbolic programming. It has evolved into a problem solving science with applications in business, engineering, and health care. One application of AI is expert system development. An expert system consists of a knowledge base and inference engine, coupled with a user interface. A crucial aspect of expert system development is knowledge acquisition and implementing computable ways to solve problems. There have been several expert systems developed in medicine to assist physicians with medical diagnosis. Recently, several programs focusing on drug therapy have been described. They provide guidance on drug interactions, drug therapy monitoring, and drug formulary selection. There are many aspects of pharmacy that AI can have an impact on and the reader is challenged to consider these possibilities because they may some day become a reality in pharmacy.

Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit

OBJECTIVE: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002. METHODS: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend …" is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest …" is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. CONCLUSION: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

Administration of enoxaparin by continuous infusion in a naturalistic setting: analysis of renal function and safety.

STUDY OBJECTIVE: To describe the clinical use and safety of continuous infusion (CI) enoxaparin in a naturalistic setting and to evaluate the influence of renal function on enoxaparin elimination. DESIGN: Retrospective medical record review. SETTING: 1000-bed tertiary care teaching centre. PATIENTS: Hospitalized patients that received enoxaparin by CI during a 2-year period. INTERVENTIONS: None. MEASUREMENTS: Specific details of dosage and monitoring were collected. Adverse drug reactions (ADR) were recorded. Creatinine clearance (CrCl) was calculated using Cockroft and Gault and Brater equations. A population pharmacokinetic analysis was performed using the non-linear mixed effect model (NONMEM). For patients located in the intensive care unit (ICU) and ward, POSTHOC pharmacokinetic parameter estimates were evaluated using the Wilcoxon rank-sum. Pearson correlation coefficient was calculated to determine the association between renal function and anti-Xa clearance. MAIN RESULTS: Sixty-seven patients received enoxaparin by CI of which 61.2% were in the ward and 38.8% in the ICU. The average initial rate and duration of infusion were 5.2 mg/h and 5.6 days, respectively. The number of anti-Xa concentration measurements averaged five per patient. Nine patients experienced an ADR. The most frequent ADR was gastrointestinal bleeding (n = 4). Among the 67 patients, 48 had available anti-Xa concentrations and were included in the NONMEM model. The anti-Xa CL and volume of distribution for ICU and ward patients averaged 0.64 +/- 0.34 L/h, 10.6 +/- 1.55 L and 1.01 +/- 0.39 L/h, 9.08 +/- 1.17 L, respectively. CrCl was not a significant covariate when included in the NONMEM model, and the association between CrCl and anti-Xa clearance was not significant (R2 = 0.0005; P = 0.8916). CONCLUSIONS: This study is the first to report the use and safety of prolonged CI enoxaparin. Pharmacokinetic parameters of enoxaparin differ in ICU vs. ward patients. Overall, we found the safety of CI to be comparable to subcutaneous administration. Also, we found no effect of renal function on enoxaparin elimination.

Drug use in a surgical intensive care unit.

A retrospective review of drug usage in 180 patients admitted to a surgical intensive care unit was conducted. The average stay was three days and the total and daily number of drugs averaged 7.6 and 5.6, respectively. The most common drug class used was antibiotics, with cefazolin being the most commonly used antibiotic. Other commonly used drugs include analgesics, diuretics, H2-antagonists, vasoactive drugs and inotropes, antacids, and antiarrhythmics. This study indicates that patients admitted to a surgical intensive care unit are exposed to a variety of potent drugs, often given in combination over a short time period. Although further studies are needed to delineate specific aspects of drug use and patient characteristics, this study suggests that there is a need for close monitoring of drug therapy in these patients with special attention to reduction of drug costs.

Norepinephrine in septic shock: renewed interest in an old drug.

Vasopressors are the mainstay after fluids in the hemodynamic support of patients with septic shock. Although dopamine is commonly used in this situation, it is sometimes ineffective. Because of its potential adverse vasoconstrictive effects, norepinephrine usually has been chosen only when all other drugs have failed in septic shock. However, several recent reports have suggested a beneficial effect of norepinephrine, often in doses higher than those commonly used. Specifically, these studies in 77 patients showed that norepinephrine effectively elevates blood pressure and increases systemic vascular resistance without decreasing cardiac output. Renal function in these patients appears to be maintained. Information on oxygen transport is variable; however, the mortality from sepsis remains high at between 17 and 50 percent. Until more information becomes available, norepinephrine appears to be a useful drug in maintaining blood pressure in patients with septic shock, but higher than usual doses may be needed.

Paraquat poisoning: a review.

The pathophysiology, symptoms and treatment of paraquat intoxication, primarily from oral ingestion, and the pharmacology and pharmacokinetics of paraquat are reviewed. Toxicity has occurred after topical application, oral ingestion or inhalation of paraquat. Systemic toxicity has not been reported from smoking of paraquat-contaminated marijuana but heavy abusers of contaminated marijuana may experience coughing, hemoptysis and mouth irritation. Following ingestion of 30 mg/kg or 50 ml of a 21% (w/w) solution of paraquat (as the base), hepatic, cardiac or renal failure or death may occur. Smaller doses (greater than or equal to 4 mg/kg of paraquat base) may cause respiratory distress, renal dysfunction or, occasionally, jaundice or adrenal cortical necrosis. When paraquat ingestion is suspected, the drug should be removed immediately from the gastrointestinal tract by gastric lavage or by whole-gut irrigation. Adsorbents such as Fuller's earth, bentonite or activated charcoal may be used during gastric lavage. Combined use of forced diuresis (with furosemide, mannitol and i.v. dextrose in water or normal saline), hemodialysis or hemoperfusion is recommended until the compound cannot be detected in body fluids or the dialysate. Immediate and effective treatment is necessary to prevent systemic toxicity or death from paraquat intoxication.