Epidural analgesia and liver resection: postoperative coagulation disorders and epidural catheter removal.

BACKGROUND: The aim of this study was to quantify the duration and severity of postoperative coagulopathy in order to establish the optimal time for epidural catheter removal. METHODS: In a 2-year retrospective study, 140 consecutive patients underwent major liver resection. RESULTS: Epidural catheters were present in 123 patients (87.9%). Resections were: 33 (26.8%) right hepatectomy (with or without left metastasectomy), 9 (7.3%) left hemihepatectomy (with or without right metastasectomy), 37 (30.1%) trisectionectomy (extended hemihepatectomy) and 44 (35.8%) non-anatomical metastasectomy. Surgery was quantified by segments resected (4 [range: 1-7]). Vascular inflow occlusion was used in 65.6%. Ischaemic time was 26.5 min (range: 0-104 min). Platelet count fell postoperatively and was lowest on day 2 (205±72 10(9) L(-1)). There was a significant increase in prothrombin time, activated partial thromboplastin time and International Normalised Ratio (INR) postoperatively, peaking on day 2 (21.5±5.6 s, 37.9±5.8 s and 1.9±0.5, respectively). Changes persisted beyond day 6. Epidural catheters were removed on day 5 (1-11), with a protocol criterion of INR <1.2. Actual INR on day 5 was 1.49±0.36. CONCLUSION: Despite this, no epidural or spinal haematoma was recorded.

Massive transfusion--evaluation of current clinical practice and outcome in two large teaching hospital trusts in Northern England.

BACKGROUND AND OBJECTIVES: Although numerous guidelines exist for the management of massive blood loss, there have been few data confirming whether these guidelines are observed in practice or whether compliance results in improved outcome. We have performed a retrospective audit of cases of massive transfusion in two major teaching hospital trusts in Northern England to investigate the use of blood components and patient outcome. MATERIALS AND METHODS: The massive transfusion population was electronically derived from a list of all blood component transfusions in 2006. Data from the intensive care and patient administration databases established hospital outcome. Factors independently predictive of survival were identified by logistic regression. Data are presented as medians and interquartile ranges. Odds ratios (OR) are given with 95% confidence intervals. RESULTS: Two hundred and four patients had a massive transfusion. Although only 1.3% of all transfused patients, the massive transfusion group used 10% of the total blood products. Their mortality rate was 34%. Factors independently predictive of survival were: a ratio of fresh frozen plasma: red blood cells > 1.1, OR 7.22 (1.95-26.68), and elective surgery, OR 4.56 (1.88-11.05). Factors independently predictive of death were: age (per year), OR 0.97 (0.95-0.99), liver disease, OR 0.25 (0.09-0.70), male gender, OR 0.41 (0.19-0.89), vascular surgery, OR 0.34 (0.12-0.96) and number of adult packs of platelets transfused, OR 0.69 (0.57-0.83). CONCLUSION: Massive transfusion occurs rarely but has a high mortality and requires a disproportionate amount of blood products. An increased ratio of fresh frozen plasma to red blood cells was associated with improved outcome.

Randomized clinical trial of the effects of methylprednisolone on renal function after major vascular surgery.

BACKGROUND: Perioperative renal dysfunction following abdominal aortic aneurysm (AAA) repair is multifactorial and may involve hypotension, hypoxia and ischaemia-reperfusion injury. Studies of cardiac and hepatic transplant surgery have demonstrated beneficial effects on renal function of high-dose methylprednisolone administered before surgery. METHODS: Twenty patients undergoing elective open AAA repair were randomized to receive either methylprednisolone 10 mg/kg or dextrose (control) before induction of anaesthesia. Blood was analysed for a panel of cytokines representative of T helper cell type 1 and 2 subsets. Urine was analysed for subclinical markers of renal dysfunction (albumin, alpha(1)-microglobulin and N-acetyl-beta-D-glucosaminidase). RESULTS: Data from 18 patients were analysed. Both groups demonstrated glomerular and proximal convoluted tubular dysfunction that was unaffected by steroid treatment. Steroid administration increased serum levels of urea and creatinine (both P < 0.001). The steroid group had increased interleukin 10 levels (P = 0.005 compared to controls). There were no differences between groups in overall surgical complications, length of intensive care unit (P = 0.821) and hospital (P = 0.719) stay, or 30-day mortality. CONCLUSION: Methylprednisolone administration altered the cytokine profile favourably but adversely affected postoperative renal function.

Tetanus in a subcutaneous drug abuser: ineffectiveness of intrathecal baclofen.

This report discusses the issues involved in the diagnosis and management of tetanus. A 29-year-old female with a history of illicit drug use presented with progressive tetany secondary to an abscess on her forearm from subcutaneous injections. She was managed in the intensive care unit for 29 days and was discharged to the ward. The main issue in her management was control of tetanic episodes interfering with ventilation and resistant to intrathecal baclofen. Other therapeutic strategies aimed at reducing spasms included magnesium, atracurium, pancuronium, midazolam, propofol and dantrolene. We conducted searches on Medline, PUBMED and the Cochrane Database of Systematic Reviews using the following terms: tetanus, treatment, therapy, drug abuse, magnesium, baclofen and human anti-tetanus immunoglobulin (hAIG). The current strategies involved in treating tetanus are discussed.

Effect of perioperative steroids on renal function after liver transplantation.

Subclinical renal dysfunction is thought to occur as a systemic manifestation of ischaemia-reperfusion injury of other organs. Liver transplantation is associated with major ischaemia-reperfusion injury. Thirty-four patients undergoing elective liver transplantation were randomly allocated to receive either saline or 10 mg.kg(-1) methylprednisolone on induction of anaesthesia. Urine was taken for N-acetyl-beta-D-glucosaminidase, creatinine and other markers of tubular function. Serum chemistry was measured for 7 days. Creatinine concentration increased in the saline group but not in the methylprednisolone group (p < 0.0001), with the greatest difference on the third postoperative day (mean (SD) 164.8 (135.8) mumol.l(-1)vs 88.5 (39.4) mumol.l(-1), respectively). Similar changes were seen in postoperative alanine transferase (865 (739) U.l(-1)vs 517 (608) U.l(-1), respectively; p < 0.0001) on the second postoperative day. Both groups exhibited increases in markers of renal tubular dysfunction and of glomerular permeability. Patients in the saline group sustained more adverse events (8/17 (47%) vs 2/17 (12%); p = 0.02). The data confirm increased proximal tubular lysosomal turnover, consistent with an increased tubular protein load, following liver transplantation, and suggest that methylprednisolone protects against renal and hepatic dysfunction.

Interleukin 13 and inflammatory markers in human sepsis.

BACKGROUND: Interleukin (IL) 13 is an anti-inflammatory cytokine that reduces inflammatory cytokine production, and enhances monocyte survival and MHC class II and CD23 expression. The only report of IL-13 in human sepsis noted no increase in IL-13 concentration, in contrast to animal data. This study further examined the expression of IL-13 in relation to human sepsis. METHODS: In a prospective observational study of 31 patients (24 men) with sepsis or septic shock, high-sensitivity enzyme-linked immunoabsorbent assay (ELISA) was used to quantify levels of tumour necrosis factor (TNF) alpha on admission, and on days 1, 3, 5 and 7 thereafter. IL-13 and IL-2 were assayed by standard ELISA, and HLA-DR on CD14-positive monocytes was measured by flow cytometry. RESULTS: Twenty-three patients developed septic shock. Monocyte HLA-DR levels showed greater depression and a slower recovery in shocked than non-shocked patients. The serum IL-13 concentration was significantly higher in the shocked group from admission to day 3, but subsequently decreased to levels similar to those in the non-shocked group. IL-13 concentrations were higher in non-survivors. The TNF-alpha concentration was higher in those with septic shock than in those without. The TNF-alpha level correlated with IL-13 concentration (r(S) = 0.61, P = 0.002). The IL-13/TNF-alpha ratio was greater in patients with shock than those with sepsis only (P = 0.017). IL-2 was undetectable. CONCLUSION: In human sepsis and septic shock, IL-13 correlated with TNF-alpha expression, but its effect on HLA-DR class II molecules remains unclear.

Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding.

UNLABELLED: The management of bleeding gastric varices has not been standardized. Although transjugular intrahepatic portosystemic shunt (TIPS) is used in most centers, endoscopic treatment with N-butyl-2-cyanoacrylate (cyanoacrylate) glue has recently been shown to be effective. Cost-effectiveness analyses of these methods are lacking. METHODS: We performed a retrospective review of patients with bleeding gastric varices treated either by TIPS or cyanoacrylate glue injection. Economic analysis was based on direct costs for a fixed financial year. The two groups were compared for a period of 6 months follow-up, to liver transplantation, or death for each patient. RESULTS: Between January, 1995 and December, 1999, 20 patients with bleeding gastric varices had TIPS; 23 patients had cyanoacrylate glue injection from January, 2000 to October, 2001. There were no significant differences between the two groups in patient characteristics, transfusion requirement, and gastric variceal anatomy. In the TIPS group, 15/20 patients had the procedure performed within 24 h of hemorrhage, and 90% of stent insertions were successful. Complications consisted of two cases of pulmonary edema, two cases of severe encephalopathy, and a 15% stenosis rate at 6 months. In the glue group, there were 3 +/- 1.5 endoscopies and 2 +/- 1 injections per patient, with a 96% initial hemostasis. There was one case of (glue) pulmonary embolism and one blocked front endoscope lens, which required repair. The initial rebleed rate was significantly lower in patients who had TIPS (15% vs 30%, p = 0.005). The inpatient stay was shorter in the glue group (13 +/- 1 vs 18 +/- 2 days, p = 0.05), but there was no difference in the overall mortality rate. The median cost within 6 months of initial gastric variceal bleeding was $4,138 US dollars ($3,009-$8,290 US dollars) for glue versus $11,906 US dollars ($8,200-$16,770 US dollars) for TIPS (p < 0.0001). CONCLUSION: In this comparable group of patients, cyanoacrylate glue injection was more cost effective than TIPS in the management of acute gastric variceal bleeding. A prospective, randomized trial would be required to confirm our analysis.

Motorcycle injury and survival: improving outcomes.

The aim of this study was to examine all motorcycle accident injuries presenting in Yorkshire, United Kingdom, and to assess the impact of the introduction of a consultant-led trauma team on mortality, 1993-2000. Data were collected on 1239 patients. Factors independently associated with survival by logistic regression were: the presence of abdominal trauma (odds ratio 0.46, 95% confidence interval 0.31 to 0.68), the presence of chest trauma (OR 0.41, 0.29 to 0.6), the presence of head trauma (OR 0.36, 0.30 to 0.45), requirement of a blood transfusion in the emergency room (OR 0.88/unit of blood, 0.72 to 1.07), presence of the trauma team (OR 0.43, 0.16 to 1.03) and the number of years into the program (OR 1.34/year, 1.07 to 1.67). The single factor determining improved survival was the time into the study. This shows that treatment of motorcycle trauma has improved overall with time. We propose that the introduction of uniform treatment protocols and improvements in the general standard of care have had a great effect.

Injury patterns associated with mortality following motorcycle crashes.

All patients involved in motorcycle crashes admitted to various hospitals in the Yorkshire region of UK between January 1993 and December 1999 were retrospectively reviewed to identify the factors that are likely to predict a reduced survival. Of the 1239 patients requiring hospital admission, 74 died. The probability of reduced survival was estimated by a logistic regression model using independent variables such as head injury, thoracic trauma, abdominal injury, spinal injury and pelvic fracture and a compound variable of pelvic fracture combined with a long bone fracture. The odds ratio for head injury was 0.349, chest injury 0.39, abdominal injury 0.42, and the compound variable (pelvis plus a long bone fracture) 0.576. The mean injury severity score (ISS) in the fatal group was 35.96 compared to 12.2 in the group that survived (P<0.01). There was a significant difference in the Glasgow coma scale (GCS) between patients wearing a helmet and those that did not wear any protective headgear (P=0.0007). Head injury followed by chest and abdominal trauma were found to predict a reduced survival rate. Use of helmets should continue to be compulsory. Chest and abdominal injuries should be diagnosed and treated early to reduce mortality.

Functional iron deficiency, infection and systemic inflammatory response syndrome in critical illness.

To investigate the prevalence and clinical relevance of functional iron deficiency in the critically ill, we performed a prospective observational study in a university hospital general intensive care unit. We collected patient demographics, severity of illness data, haematological and biochemical variables in 51 consecutive admissions. We recorded episodes of culture-positive infection. Functional iron deficiency (FID), measured by red cell hypochromasia on flow cytometry, was present in 35% of patients at admission to intensive care. FID patients were of similar age, diagnosis, APACHE score, sequential organ failure assessment (SOFA) score, haemoglobin, serum B12, folate and ferritin to patients without FID. However, patients with FID had a prolonged intensive care stay compared with non-FID patients (P<0.001) and increased time to hospital discharge (P=0.09). Duration of intensive care stay correlated with severity of FID (r=0.33, P<0.02). Systemic inflammatory response syndrome (SIRS) was present for longer in those with FID (P<0.02). Overall mortality did not differ between groups. No difference was seen in the incidence of positive cultures between those with FID (9/18 patients) and those without FID (15/33 patients). FID was independently associated only with abnormal white blood cell count (WBC < 4 or > 11 x 10(9) x l(-1)) at admission to ICU, P=0.007, but not with positive cultures. There is a high prevalence of FID in intensive care, associated with an increased duration of stay and duration of SIRS. We have been unable to demonstrate a link with infection, either as a predisposing factor or as an acute response.

Pulmonary artery catheterization and mortality in critically ill patients.

Pulmonary artery catheters are widely used in intensive care, but evidence to support their widespread use in sparse. Some published data suggest that greater mortality is associated with use of these catheters. The largest study to date looked at > 5500 patients in several centres in America and found a greater 30 day mortality in those patients receiving a pulmonary artery catheter. We tested the hypothesis that, on our intensive care unit, mortality was greater for those patients receiving a pulmonary artery catheter. Using a propensity score to account for severity of illness, the odds ratio for mortality in those patients receiving a pulmonary artery catheter was 1.08 (95% confidence interval 0.87-1.33). We believe that continued use of the pulmonary artery catheter is safe; a large randomized controlled trial examining outcome is unlikely to provide an adequate answer.

Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis.

OBJECTIVE: To assess the relationship between IL-10 release and anti-inflammatory response following blunt trauma. DESIGN: Prospective longitudinal clinical study. SETTING: Departments of trauma and anaesthetics in a university teaching hospital. PATIENTS: Forty-eight adult patients with a mean injury severity score of 14.5 (range 9-57) were prospectively studied following blunt trauma. MEASUREMENTS AND RESULTS: Venous blood samples were collected on arrival and at 16 and 24 h, and at 3, 5, and 7 days. Peripheral blood mononuclear cell (HLA-DR) expression on CD14 + monocytes was quantified by flow cytometry and serum IL-10 was assayed by ELISA. Anti-inflammatory response was defined as monocyte HLA-DR expression of less than 30% of that seen in healthy controls. Serum IL-10 levels in trauma patients on arrival was significantly elevated, 70.0 [48.0-92.1, 95% confidence interval, (CI)] compared to the control group, 3 (0-5) (P < 0.0001), and monocyte HLA-DR expression was significantly lower, 14.2 (12.1-16.3, 95% CI), in patients versus 25.2 (22.4-28.1) in controls (P < 0.001). Patients with low HLA-DR expression (n = 14) had significantly higher serum IL-10 levels than those whose HLA-DR expression remained above 30% of the control value (n = 34), (P < 0.038). In patients who developed sepsis (n = 11), serum IL-10 levels were greater on admission, [143.7 (80.2-207.2) pg/ml(-1)], and remained elevated during the study period compared with non-complicated patients, [50.16 (33.5-66.8) pg/ml(-1)]. Immediate IL-10 (2 h following trauma) was negatively correlated with simultaneous HLA-DR expression, (r = -0.49, P = 0.0005). CONCLUSION: These findings support the view that IL-10 release regulates monocyte HLA-DR expression and may be related to an anti-inflammatory response and development of sepsis following trauma.

Laser Doppler flowmetry is useful in the clinical management of small bowel transplantation. The Liver Transplant Group.

OBJECTIVE: Laser Doppler flowmetry (LDF) has been used as a research tool to measure splanchnic perfusion. In this report, we aim to demonstrate the clinical value of this technique in perioperative monitoring of transplanted small bowel. METHODS: A 24 year old man underwent small bowel transplantation using a previously described technique. Microvascular blood flow in the transplanted bowel was measured using an LDF splanchnic probe. Postoperatively this was applied to the stoma facilitating direct measurements of graft mucosal flow. Measurements (perfusion units (PU)) were documented prior to implantation, post-reperfusion, postoperatively, during graft ischaemia, and in response to therapeutic interventions (dopexamine and phenylephrine infusions). RESULTS: Prior to transplantation, biological zero was established. Flow at five, 15, and 60 minutes after reperfusion was 74 (1.9) PU, 87.5 (3.3) PU, and 141.5 (2.5) PU, respectively. Postoperative mucosal flow was 141.6 (2.9) PU. Subsequent LDF measurement detected absence of flow even though clinical signs suggested only moderate reduction. This was confirmed on surgical re-exploration and facilitated prompt resection of a non-viable segment. Fluid and dopexamine administration resulted in a dose dependent improvement in flow, independent of blood pressure. Addition of phenylephrine increased total mucosal flow and unmasked a cyclical component. CONCLUSION: This case demonstrates the clinical value of LDF as an "alarm" to indicate graft perfusion failure and as a monitor for therapeutic interventions. Phenylephrine and dopexamine may both be of value in improving mucosal flow in the transplanted small bowel.

Interleukin-10 release and monocyte human leukocyte antigen-DR expression during femoral nailing.

This study determined the effect of femoral nailing on the expression of monocyte Class II antigens and interleukin-10 release and sought to differentiate any differences in the release of these elements of immune reactivity in patients undergoing reamed and unreamed nailing. Thirty-two patients presenting with an acute femoral fracture were studied. In 15 patients, the femoral fracture was stabilized with a reamed technique and in 17 patients with an unreamed technique. Venous blood samples were taken at presentation, at anesthetic induction, immediately after nail insertion, and subsequently at 1, 4, and 24 hours and at 3, 5, and 7 days after surgery. Serum interleukin-10 was measured by an enzyme-linked immunosorbent assay, and monocyte human leukocyte antigen-DR expression was quantified by flow cytometry. Serum interleukin-10 release and human leukocyte antigen-DR expression on monocytes showed a clear response to the nailing procedure. The group of patients undergoing a reamed femoral nailing procedure showed significantly higher interleukin-10 release and a significant depression in the expression of human leukocyte antigen-DR on monocytes compared with those whose nail had been inserted unreamed. One patient in the reamed femoral nailing group died of adult respiratory distress syndrome 3 days after injury. Reamed intramedullary nailing appears to be associated with greater impairment of immune reactivity than is the unreamed nailing technique.

Ex vivo and in situ resection of inferior vena cava with hepatectomy for colorectal metastases.

OBJECTIVE: To describe the surgical techniques and early results of inferior vena cava (IVC) resection in patients with advanced liver tumors. SUMMARY BACKGROUND DATA: Involvement of the IVC by hepatic tumors, although rare, is considered inoperable by standard resection techniques. Concomitant hepatic and IVC resection is required to achieve adequate tumor clearance. METHODS: Between February 1995 and February 1999, 158 patients underwent hepatic resection for colorectal metastases in the authors' unit. Eight patients, aged 42 to 80 years (mean 62 years), with hepatic metastases from colorectal cancer underwent concomitant resection of the IVC and four to six hepatic segments. Resections were carried out under total hepatic vascular exclusion in four patients and ex vivo in four patients. Between 30 degrees and 360 degrees of the retrohepatic IVC was resected and replaced with an autogenous vein patch (n = 1), a ringed Gore-Tex tube graft (n = 2), a Dacron tube graft (n = 1), or a patch (n = 3) or was repaired by primary suturing (n = 1). RESULTS: There were two early deaths from multiple organ failure. One patient survived 30 months after ex vivo resection but died of renal cell carcinoma, and another died with recurrent disease at 9 months. The remaining four patients remained alive 5 to 12 months after surgery, with no hepatic failure or venous obstruction; tumor recurrence was present in two. Nonthrombotic occlusion of the neocava occurred in one patient and was stented successfully. CONCLUSIONS: Although concomitant hepatic and IVC resection is associated with a considerable surgical risk, this aggressive surgical approach offers hope for patients with hepatic tumors involving the IVC, who would otherwise have a dismal prognosis. This procedure can be performed under total hepatic vascular exclusion, with or without venovenous bypass, and by ex vivo bench resection.

A randomized trial of solvent/detergent-treated and standard fresh-frozen plasma in the coagulopathy of liver disease and liver transplantation.

BACKGROUND: Virus inactivation of pooled fresh-frozen plasma (FFP) by the solvent/detergent (SD) method results in a loss of approximately 20 percent of factor VIII. This study aimed to assess the efficacy of SD-treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation. STUDY DESIGN AND METHODS: Forty-nine patients with coagulation deficits due to liver disease, who required FFP for invasive procedures or liver transplantation, were randomly assigned to receive either FFP or SD-treated plasma. Patients were assessed for side effects, correction of coagulopathy over 24 hours, and seroconversion for viral markers 6 to 18 months after treatment. RESULTS: In the liver disease group, equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD-treated plasma, with a similar return to baseline values over 24 hours. There was greater correction of the International Normalised Ratio in patients receiving SD-treated plasma (p = 0.037), but this patient group had higher baseline values than recipients of FFP (p = 0.024). Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD-treated plasma. The use of other blood components during transplantation was identical in the two treatment groups. No seroconversions were seen for HIV or hepatitis B or C virus. One patient who had received FFP seroconverted for human parvovirus B19. Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies, as later testing of these patients gave negative results. Minor side effects were rare in both groups. CONCLUSION: SD-treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation. Assessment of seroconversion for viral markers in recipients of plasma-derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected.

Extravascular lung water and acute respiratory distress syndrome--oxygenation and outcome.

We studied eleven consecutive patients to assess the influence of extravascular lung water on clinical outcome. All patients were mechanically ventilated using a standardized protocol. Inspired oxygen concentration was adjusted to an initial target PaO2 of greater than 8.0 kPa (60.8 mmHg). All patients received inhaled nitric oxide (NO) at a concentration of 20 ppm. Extravascular lung water index (EVLWI) was measured by a dual indicator technique (COLD Z-021 monitoring system, Pulsion, Munich, Germany). Patients were managed with fluids and inotropes according to a standard protocol. Median age was 45 (range 27-60) years, mean APACHE II score on admission 31 (range 17-36), duration of mechanical ventilation 15 (range 6-28) days, mean admission Murray lung injury score 2.5 (range 2-3) and admission EVLWI 20.8 (range 8.7 to 54.7) ml.kg-1. The only variables independently predictive of PaO2/FiO2 ratio were serum albumin (B = 1.7 +/- 1.61) and EVLWI (B = -2.1 +/- 0.47), r2 = 0.33, P < 0.0001. In severe ARDS, (PaO2/FiO2 < 150 mmHg), mean EVLWI was 24.4 (22.4 to 26.4, 95% confidence intervals) ml.kg-1 compared with 15.1 (12.2 to 18.0) ml.kg-1 during moderate ARDS (P < 0.001). Serum albumin likewise differed, 29.4 (27.6 to 31.2) vs 35.1 (31.8 to 38.4) g.l-1, P < 0.005. PAOP was higher during periods of poor oxygenation, 12.7 (11.9 to 13.5) vs 9.3 (7.9 to 10.7) mmHg, P < 0.001. The four survivors had greater initial EVLWI than non-survivors, 31 (24.1 to 37.9) vs 20.7 (16.0 to 25.4) ml.kg-1, P = 0.034 and showed a greater reduction in lung water, 15.2 (9.3 to 21.1) vs 5.4 (2.1 to 8.7) ml.kg-1, P = 0.013.