Central venous catheter infections: concepts and controversies.

Central venous catheters (CVCs) are widely used in critically ill patients in intensive care units. However, infectious complications are common and may limit their utility. We critically review the literature to determine the impact of CVC design and composition, insertion site selection, insertion procedures, care and removal of temporary CVCs on infectious complications. Relevant articles were identified and selected for review using a database search (Medline and manual of the English language literature) based upon study design and sample size with an emphasis on prospective randomized trials. To minimize infectious complications and maintain a reasonable cost-benefit ratio, we recommend: i) use a single lumen catheter unless clear indications for a multi-lumen catheter exist; ii) insert the catheter via the subclavian vein if no relative contraindication exists (bleeding diathesis, positive pressure ventilation); iii) disinfect the insertion site employing sterile technique; iv) apply a dry, sterile dressing and change the dressing every other day; v) inspect the insertion site for signs of infection and remove the catheter if pus is present; vi) if a catheter-related infection is suspected, change the catheter over a guidewire and culture the distal segment. The replacement catheter should be removed if an original catheter segment culture is positive.

The effects of amrinone and calcium chloride on pulmonary vasculature and biventricular function in ethchlorvynol-induced lung injury in sheep.

The effects of amrinone and CaCl2 on pulmonary vasculature and biventricular function in sheep with acute lung injury (ALI) were studied. Seven sheep were ventilated with a tidal volume of 10-12 ml.kg-1 with end-tidal CO2 of 40 +/- 5 mmHg (5.3 +/- 0.7 kPa) after acute lung injury was induced with up to 30 mg kg-1 of ethchlorvynol (ECV). Biventricular function and hemodynamic profiles were estimated with a rapid computerized thermodilution method and modified pulmonary artery catheters after acute lung injury, following a loading dose (1 mg kg-1) and maintenance dose (5 micrograms kg-1 min-1) of amrinone and after a bolus dose of CaCl2 (20 mg kg-1). ECV successfully induced acute lung damage in sheep, causing significant increases in pulmonary artery pressure (PAP) and pulmonary vascular resistance index (PVRI). Amrinone reversed the unfavorable changes induced by ECV, significantly reducing PAP, PVRI and left ventricular end-diastolic volume (LVEDV). CaCl2, however, reversed the effect of amrinone and increased PAP, PVRI, and LVEDV but decreased left ventricular ejection fraction.

Chronic upper lobe cavitary lung disease.

Chronic upper lobe cavitary lung disease may be caused by infections, emphysema, cystic fibrosis, lung cancer, sarcoidosis and rheumatologic syndromes. The diagnostic evaluation includes a complete history, a physical examination, a chest radiograph, and sputum examination and culture. In some cases, computed tomographic scanning and biopsy are required.

Systemic hemodynamic and cardiac function changes in patients undergoing orthotopic liver transplantation.

The objective of this study was to determine the changes in systemic hemodynamics (systemic vascular resistance [SVR], cardiac output [CO], systemic blood pressure [SBP]) and cardiac function (pulmonary artery pressure [PAP] and pulmonary wedge pressure [PWP]) during the 96 hours following orthotopic liver transplantation (OLT) and correlate these with changes in hepatic and renal function and patient outcome. The study took place in a 12-bed medical respiratory intensive care unit in a large teaching hospital. Twenty-one patients had OLT performed over a 21.5-month period (January 1988 to October 15, 1989) for end stage liver disease (ESLD) from a variety of causes. A flow-directed right heart catheter and an indwelling arterial cannula were inserted for hemodynamic monitoring over a 96-hour postoperative period. Liver and renal function studies, total serum calcium, serum albumin, and fluid balance were determined daily. The SVR increased significantly to 12.8 +/- 0.6 U at 48 hours compared with immediate (less than 8 hours) postoperative levels (p less than 0.05) and remained elevated for 96 hours. The CO fell progressively and was significantly lower than baseline values from 64 to 96 hours. There was significant inverse correlation between the increase in SVR and the fall in CO (r = .85, p less than 0.01). The SBP was stable except for a small, but significant fall at 16 and 24 hours postoperatively. The PWP increased significantly from a baseline value of 12.5 +/- 0.9 mm Hg to 15 +/- 0.9 mm Hg at 32 hours and remained elevated through 96 hours (p less than 0.05). The serum bilirubin level fell progressively postoperatively and the prothrombin time and partial thromboplastin time (PTT) shortened significantly. Bile flow increased progressively from 107 +/- 120 ml/24 hours at the end of the first 24 hours to 188 +/- 125 ml/24 hours by 96 hours postoperatively. Five patients died from nine to 43 days postoperatively. These patients' hemodynamic parameters were not significantly different from the patients who survived. Successful OLT is associated with a rapid increase in SVR and a fall in CO without changes in SBP. These findings tend to parallel the improvement found in results of liver function tests. However, there is no correlation between the improvement in the hemodynamic state and long-term survival.

Relationship between cardiac output and the end-tidal carbon dioxide tension.

STUDY OBJECTIVE: To further define the relationship between cardiac output (CO) and end-tidal carbon dioxide tension (ETCO2) at various levels of systemic flow. DESIGN: Prospective, controlled laboratory investigation. SETTING: Animal laboratory. TYPE OF PARTICIPANTS: Fourteen anesthetized, intubated sheep weighing 23 to 47 kg. INTERVENTIONS: One hundred seventy-two simultaneous measurements of thermodilution CO and ETCO2 were made during controlled arterial hemorrhage. After a 30-minute baseline control period, CO was sampled from approximately 0.6 to more than 8.0 L/min during a 60- to 90-minute period of controlled hemorrhage. MEASUREMENTS: Thermodilution CO; arterial pressure using fluid-filled plastic 14-gauge catheters; ETCO2 using an infrared analyzer. MAIN RESULTS: A plot of CO versus ETCO2 suggested that the relationship was logarithmic rather than linear. Linear regression showed that ETCO2 was significantly related (r = .91; P less than .001) to a logarithmic transformation of the CO. CONCLUSIONS: The relationship between CO and ETCO2 is logarithmic. Decreased presentation of CO2 to the lungs is the major, rate-limiting determinant of the ETCO2 during low flow. As the CO increases during resuscitation from shock or cardiac arrest, respiration becomes the rate-limiting controller of the ETCO2 (after the tissue washout of CO2 has occurred). Under such conditions, the ETCO2 provides useful information about the adequacy of ventilation provided that there is little ventilation/perfusion mismatch.

Fatal Cunninghamella bertholletiae infection in an immunocompetent patient.

The first fatal Cunninghamella bertholletiae infection in a clinically immunocompetent host is reported. This case differs from previously reported cases by the lack of extensive vascular invasion and thrombosis.

Mediastinal pseudocyst associated with chronic pleural effusions.

We present a patient who had chronic, bilateral pleural effusions without evidence of parenchymal, retrocardiac or mediastinal masses. A CAT scan of the abdomen and chest revealed the extension of a large abdominal pseudocyst through the diaphragm into the posterior mediastinum. The pseudocyst resolved with conservative management.

Pulmonary hypertensive response to foreign body microemboli.

Pulmonary hypertension and foreign body granulomas are recognized sequelae of chronic intravenous drug abuse. We have recently described the development of transient pulmonary hypertension and increased permeability pulmonary edema after the intravenous injection of crushed, suspended pentazocine tablets in both humans and dogs. To determine the role of vasoactive substances in the development of this transient pulmonary hypertension, we measured pulmonary hemodynamics and accumulation of arachidonic acid metabolites in dogs during the infusion of indomethacin, a cyclooxygenase inhibitor, diethylcarbamazine (DEC), a lipoxygenase inhibitor, and FPL 55712, a receptor antagonist for leukotriene C4/D4 (LTC4/D4). Following the intravenous administration of crushed, suspended pentazocine tablets (3-4 mg/kg of body weight), mean pulmonary artery pressure increased from 14 +/- 2 mmHg to 30 +/- 6 mmHg (p less than 0.05) at 60 secs with a concomitant increase in plasma concentrations of 6-keto-PGF1 alpha from 187 +/- 92 pg/ml to 732 +/- 104 pg/ml and thromboxane B2 from 206 +/- 83 pg/ml to 1362 +/- 117 pg/ml (both p less than 0.05). Indomethacin prevented the increase in both cyclooxygenase metabolites, but had no effect on the pulmonary hypertension. In contrast, DEC had no effect on the increase in cyclooxygenase products, but blocked the pulmonary hypertension. FPL 55712 did not effect either the increase in cyclooxygenase metabolites or the pulmonary hypertension. We conclude that the transient pulmonary hypertension, induced by the intravenous injection of crushed, suspended pentazocine tablets, is not mediated by cyclooxygenase products but may be mediated by lipoxygenase product(s) other than LTC4/D4.

In vivo interleukin-2 activated sheep lung lymph lymphocytes increase ovine vascular endothelial permeability by non-lytic mechanisms.

Therapeutic doses of recombinant interleukin-2 (rIL-2) often result in systemic toxicity consistent with increased vascular permeability. rIL-2 activated lymphocytes (IALs) may produce endothelial dysfunction and have cytolytic potential. However, much of the data on IAL cytotoxicity comes from the use of in vitro activated IALs. Alternatively, rIL-2 may enhance permeability directly or via release of various cytokines by host effector cells. The cytotoxicity of in vivo activated lung lymph lymphocytes has been studied in an ovine model of rIL-2 toxicity. The in vivo IALs had no significant endothelial cytolysis at effector to target ratios of 100:1. However, the in vivo IALs increased endothelial monolayer permeability to albumin, dependent on the concentration of IALs. rIL-2 induced no endothelial cytolysis or permeability alterations at doses of 10(5) and 2 x 10(5) U/ml, respectively. These findings suggest that the acute endothelial dysfunction characteristic of the vascular leak syndrome is not due to rIL-2 directly, but is mediated by in vivo IALs via non-cytolytic mechanisms and/or the release of secondary cytokines in response to rIL-2.

Inotropic and vasoactive drug treatment of interleukin 2 induced hypotension in sheep.

The side effects associated with recombinant interleukin 2 administration, including systemic hypotension and a vascular leak syndrome, may limit therapy before reaching maximum doses of this innovative and promising treatment for cancer. In an attempt to reverse this hypotension without decreasing cardiac output and systemic oxygen delivery (DO2), we studied several inotropic agents, dobutamine, dopamine, amrinone, CaCl2, and a pure alpha-adrenergic vasoconstrictor, methoxamine. These were administered singly or in combination to sheep with chronically implanted arterial and pulmonary artery catheters following 24 h of 3 x 10(5) units/kg recombinant interleukin 2. Compared to baseline values, 24 h of recombinant interleukin 2 infusion caused a significant increase in cardiac output from 4.4 +/- 0.9 (SD) to 5.0 +/- 0.6 liters/min, a significant fall in systemic vascular resistance (SVR) from 21 +/- 7 to 15 +/- 5 units, a decrease in mean systemic blood pressure (SBP) from 88 +/- 9 to 78 +/- 6 mm Hg, and a decrease in left ventricular stroke work from 51.5 +/- 8 to 49 +/- 6 gram meters (P less than 0.05) without any change in DO2. Dopamine, dobutamine, and CaCl2 returned SBP to baseline values by increasing cardiac output without increasing SVR. Methoxamine increased SBP by increasing SVR, but cardiac output decreased significantly. A combination of 12 micrograms/kg/min of dopamine and 2 to 3 mg of methoxamine infused over 15 min resulted in an increase in SBP, cardiac output, and SVR to baseline values while maintaining DO2 and oxygen consumption (VO2). We suggest that this latter combination would be appropriate for clinical use since it returns physiological parameters to normal.

Pulmonary response to foreign body microemboli in dogs: release of neutrophil chemoattractant activity by vascular endothelial cells.

Pulmonary hypertension and foreign body granulomas are complications of the chronic intravenous injection of crushed, suspended pentazocine (Talwin) tablets. To evaluate the early cellular mechanisms underlying the response of the lung to foreign body microemboli, we examined lung histopathology and bronchoalveolar lavage (BAL) fluid in dogs for accumulation of inflammatory cells shortly after the injection of crushed, suspended pentazocine tablets. We found that the injection of suspended pentazocine tablets is associated with the rapid accumulation of neutrophils around intravascular talc crystals but not within the alveolar airspaces. To determine the cause of the observed neutrophil accumulation, we assayed plasma and lavage fluid for neutrophil chemoattractant activity (NCA). NCA appeared in pulmonary arterial (PA) and left ventricular (LV) plasma within 60 s of injection of the suspended tablets. However, there was no evidence of NCA in BAL. To determine whether appearance of chemoattractant activity found in plasma was modified by inhibitors of arachidonic acid metabolism, we infused dogs with indomethacin, diethylcarbamazine (DEC), or FPL 55712 and assayed plasma for NCA after the injection of suspended pentazocine tablets. We found that the appearance of NCA is prevented by the infusion of either DEC or FPL 55712 but not by the infusion of indomethacin. We found that cultured pulmonary arterial or aortic endothelial cells also release NCA when incubated with either the suspended pentazocine tablets or talc. Extraction with acidified diethyl ether partitioned all the NCA into the organic phase. The release of NCA from cultured endothelial cells was likewise prevented by coincubation with DEC or FPL 55712 but not by coincubation with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonspecific cytotoxicity of recombinant interleukin-2 activated lymphocytes.

The administration of interleukin-2 (IL-2) and lymphokine activated killer (LAK) cells to patients with advanced metastatic cancer has yielded encouraging results. The purported ability of LAK cells to be discriminatively tumoricidal, thus sparing normal host tissue, represents a major advance over conventional chemotherapy. However, IL-2 adoptive immunotherapy results in dose-limiting toxicity characterized by weight gain, dyspnea, ascites, and peripheral-pulmonary edema suggestive of a vascular leak syndrome. It is unclear whether the observed toxicity is directly related to IL-2 and/or LAK cells. The authors examined the cytolytic nature of human LAK cells against human endothelial, epithelial, and fibroblast cell lines. Bovine endothelial cells also were studied. Using a 51Cr release assay, the cytolytic potential, time course, and effect of reactive oxygen intermediate inhibitors were studied. LAK cells were uniformly toxic against all cell lines, in contrast to high dose rIL-2 and excipient. Significant cytolysis was observed within 30 minutes and increased over the first 2 hours of LAK cells coming in contact with target cells. Reactive oxygen intermediate inhibitors did not reduce cytolytic activity. The authors thus found human LAK cells to be rapidly cytolytic against a variety of human and bovine cell lines. This cytolysis was independent of reactive oxygen intermediates.

Hypercarbic arterial acidemia following resuscitation from severe hemorrhagic shock.

Arteriovenous pH and PCO2 gradients can develop during low cardiac output states. We have seen a transient rise in arterial PCO2 and a fall in arterial pH in humans receiving closed-chest cardiopulmonary resuscitation immediately following restoration of spontaneous circulation. Using a hemorrhagic shock model in sheep, serial arterial and mixed venous blood gases were sampled and CO2 elimination was measured. When cardiac output was less than 30% of the baseline value and the arteriovenous PCO2 difference was greater than 20 mmHg, the animals were rapidly resuscitated with intravenous 0.9% NaCl and dopamine. Following resuscitation, there was a transient arterial acidosis and hypercarbia due to passage of venous blood with a high CO2 content into arterial blood. The clinical implications in the setting of hemorrhagic shock are that (1) arterial blood gases are poor indicators of the systemic acid-base state, (2) arterial blood gases drawn immediately following volume resuscitation may be misinterpreted and should probably not be used to guide therapy and (3) there is a transient hypercarbic arterial acidosis following volume resuscitation that may have deleterious effects on cardiac and cerebral function in the early post-resuscitative period.