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Biomedical subjects

J Lipman

Publications and source records attributed to J Lipman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cerebrospinal fluid penetration of high doses of intravenous ciprofloxacin in meningitis.

Nosocomial meningitis due to gram-negative organisms is a difficult clinical problem to manage because of both antibiotic resistance and poor penetration of many antimicrobials across the blood-brain barrier. Ciprofloxacin has potential in treating this condition when used in high doses. We investigated the plasma and cerebrospinal fluid (CSF) levels of ciprofloxacin in a patient with Pseudomonas aeruginosa meningitis who was treated with 400 mg of intravenous ciprofloxacin every 8 hours. Ciprofloxacin levels in plasma peaked at 10.29 mg/L without resulting in accumulation (8-hour trough levels, <1 mg/L), whereas the CSF level increased to 0.9 mg/L. This CSF level was confirmed to be similar 1 week later. After 1 week of therapy, during which there were no side effects attributable to ciprofloxacin, the organism was eradicated, and there was some clinical improvement. We recommend that 400 mg of intravenous ciprofloxacin every 8 hours be considered for treatment of difficult-to-treat gram-negative bacillary meningitis.

Aged↗
PubMed2000

Subcutaneous oxygen tensions provide similar information to ileal luminal CO2 tensions in an animal model of haemorrhagic shock.

OBJECTIVES: The cutaneous and splanchnic circulations undergo early vasoconstriction in shock. Methodological problems and insufficient information on subcutaneous carbon dioxide partial pressures limit the usefulness of previous studies on splanchnic and subcutaneous gas tensions in shock. Little comparative data exist on the responses of these tissues to shock and resuscitation. We therefore compared continuous subcutaneous PO2 (PO2sc) and PCO2 (PCO2sc) with simultaneous continuous gut luminal PCO2 (PCO2gi) in an animal model of haemorrhagic shock and resuscitation. DESIGN: Prospective observational study. SETTING: Intensive care laboratory in a teaching hospital. SUBJECTS: Five anaesthetised rats. INTERVENTIONS: Electrochemical-fiberoptic gas sensors inserted into Silastic tubing placed in the subcutaneous tissue and in the ileal lumen measured PCO2sc, PO2sc and PCO2gi continuously in five anaesthetised rats. After steady state conditions, hypotension [mean arterial blood pressure (MAP) 40 mmHg] was induced by controlled haemorrhage. The rats were allowed to remain hypotensive for 15 min and then resuscitated with shed blood and crystalloids. Arterial plasma lactate concentrations were measured at defined periods during the study. MEASUREMENTS AND MAIN RESULTS: Hypovolaemia resulted in a significant decrease in PO2sc (P < 0.01) and a significant increase in PCO2gi and PCO2sc (P < 0.05). These values returned to baseline with resuscitation. PO2sc appeared to respond to haemorrhage earlier than PCO2gi and PCO2sc (P = 0.02). PO2sc was inversely correlated with PCO2gi (r2 0.7, P < 0.001). There were no significant changes in arterial plasma lactate concentrations. CONCLUSIONS: In our rat model, subcutaneous oxygen tension provided similar information to ileal luminal PCO2 and was more rapidly responsive than subcutaneous carbon dioxide tensions and arterial lactate during evolving haemorrhagic shock and resuscitation.

Animals↗
PubMed2000

The treatment of tetanus with intrathecal baclofen.

The treatment of severe tetanus generally requires prolonged mechanical ventilation. We describe two cases managed with continuous intrathecal infusion of baclofen via a subcutaneous tunnelled spinal catheter and an abdominal injection port. Baclofen, by diminishing spasms and spasticity, allowed reduced sedation and paralysis requirements. This potentially decreases the time and resources required for intensive care management. Complications include sedation, hypotension and CSF infection. After appropriate dose adjustment, baclofen improves the management of severe tetanus.

Aged↗
PubMed2000

Can we achieve consensus on central venous catheter-related infections?

Central venous catheter-related bacteraemia is a substantial and preventable source of iatrogenic morbidity and mortality. A single episode of catheter-related bacteraemia has an estimated cost of A$50,000, with an attributable mortality between 10 and 35%. Catheter colonization is diagnosed with standard culture techniques. Diagnostic criteria for catheter-related bacteraemia include the results of cultures from the catheter tip, the peripheral blood and other possible sites of infection. The presence of clinical symptoms and subsequent defervescence may assist in making the diagnosis. This review explores the existing definitions of catheter-related infections and proposes a new and more rigorous classification with criteria for definite, probable and possible catheter-related bacteraemia. The authors hope that this classification will enhance the interpretation of the literature and the planning of new investigations. Infection rates can be reduced by appropriate site selection, adequate skin preparation, sterile technique and appropriate dressings. Decreased manipulation of administration sets, with more careful technique and less frequent set replacement, may reduce hub contamination. Infection rates increase with the duration in situ of the catheter, however are not reduced by regular scheduled catheter replacement or guide-wire exchanges. A range of antimicrobial catheter materials and coatings are under investigation, some of which are effective in reducing the rate of catheter-related bacteraemia. Chorhexidine-silver sulphadiazine and rifampicin-minocycline are the best studied combinations to date. Further developments are expected, although none are likely to be as effective as not inserting or removing the central venous catheter when it is not required.

Anti-Infective Agents↗
PubMed2000

Towards better ICU antibiotic dosing.

OBJECTIVE: To review the recent pharmacokinetic and pharmacodynamic reports of some of the commonly used antibiotics in critically ill patients and recommend alterations in their administration to improve their efficacy. DATA SOURCES: Relevant articles and published reviews on aminoglycoside, third and fourth generation cephalosporins, vancomycin and ciprofloxacin dosing in critically ill patients. SUMMARY OF REVIEW: Antibiotic regimens are derived from non-critically ill volunteers. To optimise antibiotic administration in the intensive care unit, the different 'kill-characteristics' of the antibiotic classes and the altered drug pharmacokinetics in critically ill patients should be considered together to re-evaluate the currently recommended regimens. Aminoglycosides require high peak levels to be most effective, hence large single daily doses are important. With the increased clearances in the critically ill patient, particularly those who have normal renal function, a more frequent administration than single daily dosing may be optimal (e.g. 18-hourly). Increased clearances of beta-lactam antibiotics result in low troughs causing a reduced duration of antibiotic levels above the minimum inhibitory concentration (i.e. the suggested pharmacological target for these drugs). In critically ill patients frequent dosing or even continuous infusions of the beta-lactam antibiotics may increase their effectiveness by maintaining blood levels above the minimum inhibitory concentration (MIC) for longer periods. Vancomycin has a high volume of distribution in the critically ill patient, thus the currently recommended maximum daily dose may lead to inadequate serum levels. Suggested targets for quinolone therapy involve more than just high peak levels. A ratio of Area Under (serum) Concentration (AUC) time curve to MIC of >125 has been shown to correlate with better clinical outcomes. Ciprofloxacin when given intravenously at 400 mg 8-hourly should achieve this, which is a regimen that has been shown to be safe. CONCLUSIONS: Applying pharmacokinetic and pharmacodynamic principles to critically ill patients will lead to better antibiotic use and hopefully a better outcome.

Journal Article↗
PubMed1999

Inter observer variability of the transcranial Doppler ultrasound technique: impact of lack of practice on the accuracy of measurement.

OBJECTIVE: Published data on the observer variability with the transcranial doppler (TCD) ultrasound are limited by the use of the product moment correlation coefficient. This study was designed to quantify the intra and inter observer variability with the TCD in terms of the intra class correlation coefficient (ICC) and to assess the impact of lack of practice on the observer variability and the accuracy of data generated. METHODS: The study was performed in two phases. In phase I, three observers insonated the middle cerebral artery in 10 healthy volunteers and measured peak systolic and end diastolic cerebral blood flow velocities. In phase II, the same observers repeated the experiment on five healthy volunteers after an eight week break during which none of the observers were allowed to use the TCD system. The observers were blinded to the measurements obtained. RESULTS: The ICC for peak velocity measurement was 0.9 (0.81-0.99) in phase I and 0.85 (0.66-1.00) in phase II (p < 0.05). The ICCs for end diastolic velocity measurements for phase I and II were 0.8 (0.64-0.96) and 0.67 (0.33-1.00) respectively (p < 0.01). CONCLUSIONS: A high level of observer agreement is possible with the TCD for measurement of cerebral blood flow velocities. Lack of regular practice with the system reduces the accuracy of measurements and impacts on both measured and calculated indices.

Adult↗
PubMed1999

Small tidal volume ventilation using a zero deadspace tracheal tube.

The zero deadspace tracheal tube (ZEDS-TT) is a double-lumen endobronchial tube with a truncated bronchial limb. Functionally it is unrelated to the familiar endobronchial tube used in lung isolation surgery. It is placed in the same position as a regular tracheal tube and, by means of special connectors, one limb is used for inspiration and the other for expiration, thereby greatly reducing anatomical and apparatus deadspace. In this study, we have compared respiratory and ventilatory effects of reduction of tidal volume (VT) via a single-lumen tracheal tube and the ZEDS-TT during controlled ventilation with a Siemens Elema 900C Servo ventilator. Eleven consenting adult patients (ASA I and II) undergoing elective peripheral surgery were studied. Starting at a VT value of 10 ml kg-1, data were recorded for each tube type. VT was reduced by 2.5 ml kg-1 every 10 min and stabilized data recorded. Minute volume was kept constant by increasing ventilatory frequency at each reduction in VT. We found that the ZEDS-TT produced a significant reduction in PaCO2 and airway pressure for any VT used, while maintaining oxygenation.

Adult↗
PubMed1999

Continuous infusion ceftazidime in intensive care: a randomized controlled trial.

We randomized 18 critically ill patients to receive ceftazidime 6 g/day by continuous infusion or bolus dosing (2 g 8 hourly), each with a loading dose of 12 mg/kg ceftazidime. During the first 8 h, plasma ceftazidime concentration fell below 40 mg/L in only one patient (trough 38 mg/L) from the infusion group, compared with eight from the bolus group (2-33 mg/L) for periods ranging from 73 to 369 min. Thereafter all infusion patients remained above 40 mg/L for 40 h of study versus 20-30% of bolus patients. The pharmacokinetic and pharmacodynamic characteristics of ceftazidime suggest that continuous infusions should be clinically investigated in outcome studies.

Adult↗
PubMed1999

Low plasma cefepime levels in critically ill septic patients: pharmacokinetic modeling indicates improved troughs with revised dosing.

The pharmacokinetics of a 2-g bolus of cefepime were measured in critically ill patients with normal renal function. Variable and low trough plasma drug concentrations were found, and 8 of 10 patients had levels below the MIC at which 50% of the isolates are inhibited for Pseudomonas aeruginosa. Computer simulations predicted that continuous infusion and shorter dosing intervals would increase trough levels.

Adult↗
PubMed1999

Analgesia and sedation in the critically ill--a practical approach.

Advancements in intensive care therapy have progressed rapidly over the last two decades. Associated with this have been scientifically unsubstantiated sedation and analgesia practices in the intensive care unit. There is little consensus as to which agents are the most suitable, let alone when and how to use them. There are few, if any, placebo-controlled trials involving sedative drugs in critically ill patients. In an analysis of the literature, we have attempted to present a practical approach to sedation and analgesia practices in the critically ill patient. The aim is to present a framework upon which medical personnel managing critically ill patients can develop a strategy for their own circumstances.

Analgesia↗
PubMed1998

Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma.

The cyclin-dependent kinase inhibitor p27 is a negative regulator of the cell division cycle. It is expressed at the highest levels during the quiescent (G0) and prereplicative (G1) phases, and its degradation is required for entry into the S phase. Because lack of p27 is associated with aggressive behavior in a variety of tumors of epithelial and lymphoid origin, we used immunohistochemistry and in situ hybridization to evaluate the expression of p27 in metaplastic and dysplastic Barrett's epithelium and to assess its prognostic significance in Barrett's associated adenocarcinoma (BAA) of the esophagus. In metaplastic Barrett's epithelium, p27 protein and mRNA were restricted to the superficial third of glands in all cases and extended to the lower third in 4 cases. In contrast, expression of p27 message and protein was both increased and full-thickness, in the 23 cases with high-grade dysplasia adjacent to BAA and in carcinoma in situ. Although all invasive carcinomas had elevated levels of p27 mRNA, 45 (83%) of 54 invasive carcinomas had low p27 protein levels (<50% positive tumor cells). Low p27 protein correlated with higher histological grade (P < 0.0001), depth of invasion (P = 0.0120), presence of lymph node metastasis (P = 0.05), and survival (P = 0.0197). In addition to the nuclear staining, cytoplasmic staining of p27 was noted in 11 of 23 (48%) of cases of dysplasia and in 14 of 54 (26%) adenocarcinomas and confirmed, in a subset of cases, by subcellular fractionation of protein lysates obtained from fresh tumor tissues. Cytoplasmic localization of p27 was also associated with decreased survival (P = 0.0239). Loss of p27 conferred poor prognosis independently of proliferative index, as assessed by Ki-67 (MIB-1) immunostaining, which was not significantly different in survivors versus nonsurvivors. These results show that: (a) distribution of p27 message and protein parallel one another in metaplastic and dysplastic Barrett's epithelium, suggesting transcriptional regulation of the gene in the nonneoplastic setting; (b) p27 is inactivated in the majority of BAA as a result of either post-transcriptional modification or altered subcellular localization; and (c) loss of the cell cycle inhibitor p27 is associated with parameters of aggressive behavior and unfavorable outcome in BAA.

Adenocarcinoma↗
PubMed1998

Critical care research and pre-emptive informed consent: a practical approach used in Chris Hani Baragwanath ICU.

OBJECTIVES: 1) To establish a protocol within international and local ethical guidelines to obtain informed consent for critical care research, overcoming constraints previously described and 2) To evaluate eventual recruitment using this protocol. DESIGN: Prospective descriptive study. SETTING: Multidisciplinary ICU in a community-based university teaching hospital. PATIENTS AND PARTICIPANTS: Following approval by the University Ethics Committee and Hospital Review Board, patients admitted between January and May 1996 were assessed on weekdays for potential enrollment into existing clinical trials. Discussion with potential candidates and/or next-of-kin occurred at the earliest opportunity and informed consent was obtained preemptively. Next-of-kin was notified if enrollment subsequently occurred. We evaluated the number of patients screened, the number of potential study candidates, the number for whom consent was obtained or refused and the number subsequently enrolled. INTERVENTIONS: None RESULTS: Of 249 patients screened, 149 (60%) did not meet the inclusion criteria. Of 100 potential study candidates (40% of all patients screened), we failed to make contact with the next-of-kin in 29 cases (12% of all patients screened). Thus 71 patients or next-of-kin were counselled (28% of all patients screened). In all, 30 patients (12% of all patients screened) were subsequently enrolled into a study. CONCLUSIONS: A policy of pre-emptive informed consent enabled us to overcome some of the problems previously experienced in our unit with regards to patient enrollment in critical care research. Although overall recruitment remained low, predictions for future enrollment can be made from this study.

Algorithms↗
PubMed1998

Pharmacokinetic profiles of high-dose intravenous ciprofloxacin in severe sepsis. The Baragwanath Ciprofloxacin Study Group.

The pharmacokinetics of 400 mg of ciprofloxacin given intravenously (i.v.) every 8 h (q8h) in severely septic adults was documented in a multidisciplinary, tertiary referral intensive care unit (ICU). Sixteen evaluable patients (three pharmacokinetic profiles) without renal dysfunction and with severe sepsis were studied. Ciprofloxacin at a dosage of 400 mg given i.v. q8h was administered over 1 h. Plasma samples for assay (high-pressure liquid chromatography) were taken at timed intervals (preinfusion, at the end of infusion, and at 1, 2, 3, 5, and 7 h postinfusion) for first-dose kinetics (day 0 [D0]), D2, and between D6 and D8. All pharmacokinetic variables were calculated by noncompartmental methods. Standard intensive care was provided. Peak ciprofloxacin concentrations were as follows: D0, 6. 01 +/- 1.93 mg/liter; D2, 6.68 +/- 2.01 mg/liter; and D6 to D8 6.45 +/- 1.54 mg/liter. Trough levels were as follows: D0, 0.6 +/- 0.5 mg/liter; D2, 0.7 +/- 0.4 mg/liter; and D6 to D8 0.6 +/- 0.4 mg/liter. The areas under the concentration curves (8 h) were as follows: D0, 13.3 +/- 3.8 mg . h/liter; D2, 16.8 +/- 5.4 mg . h/liter; and D6 to D8, 15.5 +/- 4.7 mg . h/liter. No drug-related serious adverse events occurred. For 17 of 18 patients enrolled in the study, the causative organisms were susceptible to ciprofloxacin. One patient developed renal failure (non-drug related) after the administration of three doses of ciprofloxacin. One patient was infected with ciprofloxacin-resistant organisms on enrollment. Nine of 16 evaluable patients had clinical cures, and 8 had bacteriological cures. One patient developed a ciprofloxacin-resistant superinfection. In two patients the clinical course was indeterminate. Two bacteriological failures occurred. We conclude that in critically ill adults ciprofloxacin at a dosage of 400 mg given i.v. q8h is safe. Its pharmacokinetic profile provides bactericidal activity against most organisms encountered in an ICU. Except for some initial accumulation on D2, no further accumulation occurred in patients without renal failure. Ciprofloxacin should be administered i.v. at a dosage of 400 mg q8h for severe sepsis.

Adult↗
PubMed1998

Good clinical research practice: what is it and is it possible in the intensive care unit?

With the growing quest for answers to vexing dilemmas in critically ill patients, more intensive care units are embarking on clinical research. This places increasing importance on Good Clinical Research Practice (GCRP), a set of guidelines drawn up by the Pharmaceutical Industry to assist investigators in conducting ethical, reliable scientific studies. GCRP is a combination of good basic management skills allied to ethical principles for scientific research. Based on the principles of the Declaration of Helsinki, it consists of three tenets: patient protection (ethics), credible data (science) and data control. This article describes GCRP specifically relating it to the intensive care situation, illustrating some of the concepts with practical examples. With a minimum of extra time and effort these basic principles can be integrated as routine into all research projects.

Clinical Trials as Topic↗