Kriton S. Filos

Hemodynamic and analgesic profile after intrathecal clonidine in humans. A dose-response study.

Background:Epidural clonidine produces effective postoperative analgesia in humans. Observed side effects include hypotension, bradycardia, sedation, and dryness of the mouth. A recent clinical study demonstrated that 150µg intrathecal clonidine administered postoperatively as the sole analgesic agent was effective but produced hypotension and sedation. Animal studies have provided evidence of a biphasic effect on blood pressure after intrathecal clonidine administration, but no data concerning this effect in humans currently exist. This study was performed to evaluate the dose-response hemodynamic and analgesic profiles of intrathecal clonidine administered after a standard surgical intervention, without perioperative administration of additional analgesics, local anesthetics, or tranquilizers. Methods:In a randomized prospective double-blind study, 30 women who underwent elective cesarean section during general anesthesia with thiopental, nitrous oxide, and halothane were studied. Forty-five minutes after tracheal extubation, a lumbar intrathecal puncture was performed, and the patients received 150 (group 1), 300 (group 2), or 450 (group 3) µg clonidine. Postoperative analgesia was assessed on a visual analog scale at rest and after deep cough at standard time points up to 24 h. At the same time points, blood pressure, heart rate, sedation, and respiratory rate also were recorded. Results:Intrathecal clonidine decreased pain in all three groups both at rest and with coughing very shortly after injection, in a dose-dependent fashion. Clonidine 450 and 300 µg reduced pain scores significantly earlier (3rd and 6th min after intrathecal injection respectively),compared with 150 µg clonidine. Pain relief, defined as the time to first request for supplemental analgesic by patients, lasted 402 ± 75 min in group 1, 570 ± 76 min in group 2, and 864 ± 80 min in group 3; significant differences among all groups; P<0.01-0.001). Clonidine reduced mean arterial pressure compared with baseline only in group 1 (21 ± 13%, P<0.05). Delayed hypotension or bradycardia were not encountered after any of the three dose studies. Sedation was evident in all groups, but group 3 patients were significantly more sedated than group 1 and 2 patients. Respiratory rate and motor activity of the lower extremities were unaffected in all three groups (differences not significant). Conclusions:These results demonstrate dose-dependent analgesia after intrathecal clonidine at doses as great as 450 µg. The nearly immediate analgesic effect observed after intrathecal injection of 300 and 450 µg clonidine strongly argues for a spinal rather than a systemic site of action of this α2-adrenergic agonist. After 300 and 450 µg intrathecal clonidine a relative hemodynamic stability is observed, suggesting a pressor effect at peripheral sites.

Intrathecal Clonidine as a Sole Analgesic for Pain Relief after Cesarean Section

In a small number of studies and isolated case reports, intrathecally administered clonidine has been reported to relieve intractable cancer pain and to prolong spinal anesthesia induced by various local anesthetics. A double-blind placebo-controlled clinical trial was carried out in order to evaluate the effect of intrathecal clonidine on pain following cesarean section. Twenty patients who underwent elective cesarean section received, 45 min after general anesthesia, either 150 micrograms (n = 10) clonidine or saline (control group, n = 10) intrathecally. Pain scores were lower in clonidine- than saline-treated patients from 20 to 120 min after intrathecal injection, as measured by a visual pain linear analog scale (P less than 0.05). Pain relief, in terms of the first supplemental analgesic request by patients, lasted 414 +/- 128 min after intrathecal clonidine and 181 +/- 169 min (mean +/- SD) (P less than 0.01) after saline. Clonidine decreased systolic, diastolic, and mean arterial pressures compared to baseline values (P less than 0.05), but heart rate and central venous pressure were unaffected (difference not significant). Maximal reduction of systolic arterial pressure was 15 +/- 9%, of diastolic arterial pressure 22 +/- 12%, and of mean arterial pressure 18 +/- 12%. Clonidine did not affect arterial hemoglobin oxygen saturation or PaCO2. Patients in the clonidine group were significantly more sedated (P less than 0.05) and more frequently reported a dry mouth (P less than 0.01) compared to the normal saline group.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial effects of growth hormone and insulin-like growth factor I on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats

BACKGROUND This study was undertaken to investigate the effect of growth hormone (GH) and insulin-like growth factor I (IGF-I), two well-known growth factors, on bacterial translocation, endotoxemia, enterocyte apoptosis, and intestinal and liver histology in a model of experimental obstructive jaundice in rats. STUDY DESIGN One hundred six male Wistar rats were divided into five groups: I (n = 21), controls; II (n = 22), sham operated; III (n = 22), bile duct ligation (BDL); IV (n = 21), BDL and GH treatment; and V (n = 20), BDL and IGF-I administration. By the end of the experiment, on day 10, blood bilirubin was determined, and mesenteric lymph nodes, liver specimens, and bile from the bile duct stump were cultured. Endotoxin was measured in portal and aortic blood. Tissue samples from the terminal ileum and liver were examined histologically and apoptotic body count (ABC) in intestinal mucosa was evaluated. Mucosal DNA and protein content were also determined. RESULTS Bilirubin increased significantly after BDL (p < 0.001). Bile from the bile duct was sterile. In group III, MLN and liver specimens were contaminated by gut origin bacteria (significant versus group I and II, p < 0.001, respectively). GH reduced significantly positive cultures (p < 0.01), and IGF-I had no effect. BDL resulted in significant increase in portal and aortic endotoxemia (p < 0.001); treatment with GH and IGF-I reduced it (p < 0.001). Mucosal DNA and protein content were reduced in animals with BDL and after treatment with GH or IGF-I; an increase to almost normal levels was noted in DNA, but not in protein. Overall the ileal architecture remained intact in all animal groups. The ABC increased after BDL. After GH and IGF-I administration, the ABC decreased significantly, and there was no difference between GH and IGF-I treated animals. After BDL, liver biopsies displayed typical changes of biliary obstruction, which were significantly improved after administration of GH and IGF-I. CONCLUSIONS Treatment with GH and IGF-I in rats with experimental obstructive jaundice reduces endotoxemia, and it improves liver histology. Apoptosis, in the intestinal epithelium, may serve as a morphologic marker of the ileal mucosal integrity, demonstrating the proliferative potential of GH and IGF-I in cases of obstructive jaundice, and this might be of potential value in patients with such conditions.

Risk factors for KPC-producing Klebsiella pneumoniae enteric colonization upon ICU admission

OBJECTIVES To identify risk factors for KPC-producing Klebsiella pneumoniae (KPC-Kp) enteric colonization at intensive care unit (ICU) admission. Recently, the emergence and spread of KPC-producing Enterobacteriaceae in healthcare facilities has become an important issue. Understanding the extent of the reservoir in ICUs may be important for targeted intervention. METHODS A prospective observational study of all patients (n = 405) admitted to an ICU was conducted during a 22 month period. Rectal samples were taken from each patient within 12-48 h of admission and were inoculated in selective chromogenic agar. K. pneumoniae isolates were characterized by standard methodology. Antibiotic susceptibility testing (agar disc diffusion method), MIC determination (Etest), identification of carbapenemase-producing isolates (Hodge test) and determination of KPC production (boronic acid-imipenem disc test) were performed. The presence of the bla(KPC) gene was confirmed by PCR. Epidemiological data were collected from the ICU computerized database and patient chart reviews. RESULTS Upon ICU admission, 52/405 (12.8%) patients were colonized with KPC-Kp that was associated with the following risk factors: previous ICU stay (OR 12.5; 95% CI 1.8-86.8), chronic obstructive pulmonary disease (OR 6.3; 95% CI 1.2-31.9), duration of previous hospitalization (OR 1.3; 95% CI 1.1-1.4), previous use of carbapenems (OR 5.2; 95% CI 1.0-26.2) and previous use of β-lactams/β-lactamase inhibitors (OR 6.7; 95% CI 1.4-32.9). For patients previously hospitalized on peripheral wards the following risk factors were identified: duration of hospitalization prior to ICU admission (OR 1.1; 95% CI 1.1-1.3), number of comorbidities (OR 1.9; 95% CI 1.1-3.5) and number of antimicrobials administered (OR 2.1; 95% CI 1.3-3.3). CONCLUSIONS The high prevalence of KPC-Kp enteric carriage in ICU patients at admission dictates the importance of implementation of infection control measures and strict antibiotic policies prior to ICU transfer.

A dose-response study of orally administered clonidine as premedication in the elderly: evaluating hemodynamic safety.

Clonidine premedication in a dose of 5 μg/kg may be particularly well suited for elderly patients. To pursue this approach, sedation, intraocular pressure (IOP), and the hemodynamic profile of two doses of oral clonidine premedication were compared in 60 elderly patients, aged 65–82 yr, who underwent elective ophthalmic surgery under local anesthesia. Group 1 (n = 20) received placebo, Group 2 (n = 20) 150 μg of clonidine (2–2.5 μg/kg), and Group 3 (n = 20) 300 μg of clonidine (4–4.5 μg /kg) in a randomized, double-blind fashion. Decreases in mean arterial blood pressure were more pronounced and occurred earlier after 300 μg of clonidine (31.4 ± 12.1%, P < 0.001) as compared to 150 μg of clonidine (18.1 ± 10.9%, P < 0.001). Throughout the study, six patients (30%) in Group 3 (300 μg clonidine-treated group), but no patient in Groups 1 or 2, were treated at least once for hypotension (P < 0.05). Heart rate decreased significantly 18.5 ± 8.1% (P < 0.001) only after 300 μg of clonidine, Clonidine 150 μg and 300 μg decreased IOP 32.1 ± 14.3% (P < 0.001) and 47.8 ± 17.2% (P < 0.001), respectively. After 150 μg of clonidine patients were significantly more sedated as compared to those given placebo (P < 0.01) but significantly less sedated than after 300 μg of clonidine (P < 0.01), where sedation persisted more than 6 h postoperatively. These results suggest that a dose of 150 μg of clonidine, given orally 90–120 min preoperatively to elderly patients managed with local anesthesia, is as effective as a dose of 300 μg in decreasing IOP perioperatively, without causing excessive hemodynamic depression and sedation.

Effect of Oral Glutamine Administration on Bacterial Tanslocation, Endotoxemia, Liver and Ileal Morphology, and Apoptosis in Rats with Obstructive Jaundice

Postoperative complications in patients with obstructive jaundice remain increased when associated with endotoxemia and the inflammatory response due to gut barrier failure. Administration of glutamine has been proposed to maintain the integrity of the gut mucosa and thus reduce bacterial translocation (BT), but the effects of this pretreatment on apoptosis and histologic morphology of various organs affected by BT in obstructive jaundice have not been studied. We therefore studied the effects of oral glutamine supplementation on endotoxemia, BT, liver and terminal ileal morphology, and apoptosis in an experimental model of obstructive jaundice. A total of 60 male Wistar rats were randomly divided into four groups of 15 each: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL + glutamine (4.5 g/kg/day in drinking water). Ileal samples for histology, DNA and protein content, liver biopsies, mesenteric lymph nodes (MLNs) for culture, and portal and systemic blood samples for endotoxin measurements were obtained 10 days later. Compared to the controls, a significant increase in contaminated MLN and liver samples and increased endotoxemia were noted in group III (p < 0.01) but were significantly reduced in group IV (p < 0.05). Group IV also had a significantly higher number of mitoses per crypt (M/c) (p < 0.05), less apoptotic body counts (ABCs) (p < 0.05), and a higher DNA content than did group III (p < 0.05). Liver biopsies from group III displayed typical changes of large duct obstruction that significantly improved after glutamine treatment, with decreased ductular proliferation.We concluded that supplementation of oral glutamine in the presence of obstructive jaundice ameliorates BT, endotoxemia, and apoptosis and improves the ileal and liver histology.

Aprotinin Prolongs Activated and Nonactivated Whole Blood Clotting Time and Potentiates the Effect of Heparin In Vitro

This study was designed to evaluate the effect of aprotinin on activated versus nonactivated whole blood clotting time using two different on-site methods and to quantify these anticoagulant properties when compared to heparin in a controlled, in vitro environment. Blood specimens were obtained prior to heparin administration from 56 patients undergoing cardiac surgery. Specimens obtained from the first consecutive 20 patients were mixed with either normal saline (NS) or aprotinin (400 kallikrein inhibiting units (KIU)/mL), inserted into Hemochron Registered Trademark tubes containing either NS or heparin (0.3 or 0.6 U/mL) and then used to measure celite-activated (celite ACT) and nonactivated whole blood clotting time (WBCT1) using four Hemochron Registered Trademark instruments. Accordingly, specimens obtained from the second consecutive 20 patients were mixed with either NS or aprotinin, inserted into Automated Clot Timer Registered Trademark cartridges containing either NS or heparin (0.06, 0.13, or 0.25 U/mL) and then used to measure kaolin-activated (kaolin ACT) or nonactivated whole blood clotting times (WBCT2) using four Automated Clot Timer Registered Trademark instruments. Specimens obtained from the last 16 patients were mixed with either incrementally larger doses of aprotinin (0, 100, 200, 300, or 400 KIU/mL) or heparin (0, 0.12, 0.24, 0.36, 0.48, or 0.72 U/mL) and were then used for measurement of whole blood clotting time (WBCT2) using six Automated Clot Timer Registered Trademark instruments. Aprotinin significantly prolonged activated or nonactivated whole blood clotting time and potentiated the prolongation of whole blood clotting time by heparin. The linear relationship between whole blood clotting time and either heparin concentration (WBCT2 = H times 357 + 280, mean adjusted r2 = 0.88) or aprotinin concentration (WBCT2 = A times 0.97 + 300, mean adjusted r2 = 0.94) was variable among patients. On average, 200 KIU/mL of aprotinin prolonged WBCT2 to the same extent as 0.69 +/- 0.28 U/mL of heparin using linear regression models within each patient. Aprotinin significantly prolongs activated or nonactivated whole blood clotting time measurements in a dose-dependent manner. Since prolongation of whole blood clotting time by heparin is potentiated by aprotinin in vitro, aprotinins anticoagulant properties may in part account for the prolonged celite activated clotting time values observed in the presence of aprotinin. (Anesth Analg 1996;82:1126-31)

Bacterial translocation, endotoxaemia and apoptosis following Pringle manoeuvre in rats ☆

BACKGROUND Intraoperative occlusion of the hepatoduodenal ligament (Pringle manoeuvre (Pm)) is often employed for the reduction of blood loss during liver surgery. No data exist to date on the effects of Pm on mucosal barrier dysfunction, systemic bacterial translocation (BT), endotoxaemia and apoptosis. MATERIALS AND METHODS Sixty-five male Wistar rats in three groups: I (n=25) controls, II (n=20) sham operation, III (n=20) occlusion of the hepatoduodenal ligament (Pm). Tissue samples from mesenteric lymph nodes (MLNs), liver, lungs and spleen were analysed after 30 min and at 24 h. Endotoxin was measured in portal and aortic blood and routine haematological and biochemical parameters were measured before and after Pm. RESULTS No differences were found in the blood parameters before and after Pm, but a significant increase in contaminated MLNs and liver was noted. All cultured bacteria were enteric in origin. Portal and aortic endotoxin were significantly increased. Overall the ileal architecture remained intact in all specimens studied and no significant pathology was observed. The ABC increased after Pm significantly (P<0.01). CONCLUSION Normothermic Pm of 30 min duration results in immediate and delayed gut barrier failure by significantly increasing BT and endotoxaemia which might be attributed to portal stasis leading to intestinal congestion as well as temporary liver ischaemia. Apoptosis increased significantly 30 min after performing the Pm.

KPC-producing Klebsiella pneumoniae enteric colonization acquired during intensive care unit stay: the significance of risk factors for its development and its impact on mortality

A prospective observational study of 226 intensive care unit (ICU) patients was conducted during a 25-month period. Rectal samples were taken at day 1, 4, and 7 and, afterwards, once weekly. Klebsiella pneumoniae was identified using standard techniques, whereas the presence of bla(KPC) gene was confirmed by PCR. During ICU stay, 72.6% of the patients were colonized with Klebsiella pneumoniae carbapenemases (KPC)-producing K. pneumoniae (KPC-Kp). Male gender, prior bed occupants, and patients in nearby beds colonized with KPC-Kp, tracheotomy, number of invasive catheters inserted, and number of antibiotics administered were the major risk factors for KPC-Kp colonization. ICU mortality (35.4%) was significantly related to Simplified Acute Physiology II score and respiratory insufficiency upon admission, cortisone administration, aminoglycoside administration, confirmed KPC-Kp infection, and severe sepsis or septic shock. The high prevalence of KPC-Kp enteric carriage in ICU patients and the significant mortality associated with KPC-Kp infection dictate the importance of early identification and isolation of such carriers.

Dissemination of two international linezolid-resistant Staphylococcus epidermidis clones in Greek hospitals

mutations, multilocus sequence typing, Greece,staphylococciSir,The growing number of infections caused by multidrug-resistantStaphylococcus epidermidis has necessitated the use of newantimicrobials, such as linezolid, and enhanced the emergenceof linezolid-resistant S. epidermidis strains. To date, mutations ofregion V of 23S rRNA (G2447T, T2504A, C2534T, G2576T,G2603T and G2631T) have been associated with the expressionof linezolid resistance among clinical staphylococcal isolates.