Joan Beltran

Moderate primary pulmonary hypertension in patients undergoing liver transplantation.

Primary pulmonary hypertension (PPH) in patients with hepatic cirrhosis is often considered an unacceptable condition for liver transplantation because of increased morbidity and mortality during the procedure.We studied the incidence, characteristics, and final outcome of patients with PPH undergoing liver transplantation in our institution. Among the 226 patients undergoing 257 liver transplantations, eight (3.5%) fulfilled the conditions of PPH and responded to vasodilator therapy. Nitroglycerin 1.5 micro gram/kg produced a decrease in pulmonary vascular resistance index (PVRI) and mean pulmonary arterial pressure (MPAP) of 20% and 15%, respectively. Patients with PPH when compared with a matched group of patients without PPH had markedly increased hemodynamic changes in PVRI (P = 0.004) and MPAP (P = 0.0001) during and after the procedure. All patients with PPH required pulmonary vasodilator therapy after reperfusion of the new liver, while none in the group of patients without PPH required this therapy. Furthermore, after graft reperfusion, patients with PPH in which venovenous bypass was not used (n = 3), had a more compromised right ventricular function with a greater increase of central venous pressure (CVP) (90%) and MPAP (140%) when compared with patients with bypass or preservation of the recipients vena cava (n = 5) in whom the increase of CVP and MPAP was 50% and 60%, respectively. Moderate PPH without a fixed level of pulmonary hypertension in patients undergoing liver transplantation is not related to an adverse outcome. (Anesth Analg 1996;83:675-80)

Evaluation of Ischemic Injury during Liver Procurement from Non-Heart-Beating Donors

The aim of this study was to assess liver viability after different periods of cardiac arrest and the predictive value of two markers of ischemia-reperfusion injury. Methods: A pig liver transplantation model of non-heart-beating donors was studied. Four donor groups were designed; three groups were submitted to different periods of cardiac arrest (20, 30 and 40 min), and the fourth group served as the control group (without cardiac arrest). In the non-heart-beating donor groups, normothermic recirculation was established 30 min prior to total body cooling. Aminotransferase, α-glutathione-S-transferase, and hyaluronic acid determinations as well as liver biopsies, were serially performed. Results: Although hepatocellular function could be preserved after 40 min of cardiac arrest, histological lesions at 5 days were considered irreversible due to the presence of a necrotic biliary tract. An overall significant relationship was found between the time period of cardiac arrest (20, 30 or 40 min) and the levels of hyaluronic acid (p = 0.004) or α-glutathione-S-transferase (p = 0.01) obtained during liver procurement and transplantation. Conclusions: The period of cardiac arrest is the determinant factor of liver viability after liver transplantation from non-heart-beating donors. As early markers of endothelial or hepatocellular damage, hyaluronic acid or α-glutathione-S-transferase levels may help to evaluate the ischemic injury of a potential donor.

An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation

BACKGROUND: Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT.

Prolonged pneumoperitoneum at 15 mmHg causes lactic acidosis

AbstractBackground: Acute increases in intraabdominal pressure (IAP) induce systemic and regional circulatory changes. Besides, mechanical compression on the capillary beds may decrease oxygen availability to the tissues. The purpose of this clinical study was to analyze the effects of increased IAP on acid-base disturbances and plasma lactate levels during prolonged carbon dioxide pneumoperitoneum. Methods: Twenty-eight patients undergoing laparoscopic sigmoidectomy were included in this study. Fourteen of them (group A) had IAP of 15 ± 1 mmHg while the remaining 14 (group B) had IAP of 10 ± 1 mmHg. The control group included six patients undergoing conventional sigmoidectomy. Results: A progressive significant increase in PaCO2 was observed in the laparoscopic groups (p < 0.01). Plasma lactate levels in group A significantly increased 90 min after insufflation (p < 0.05) and reached the highest value 1 h after deflation (9.9 ± 1 vs 31.9 ± 2.5 mg/dl, p < 0.005). Simultaneously, arterial pH decreased in all groups; however, at 1 h after surgery, it was significantly lower (p= 0.02) in group A. There was a significant correlation between acid concentration due to lactate and lactate concentration (GA: R2= 0.717, p= 0.03; GB: R2= 0.879, p= 0.006 and GC: R2= 0.853, p= 0.008). Conclusion: High IAP causes lactic acidic accumulation in patients undergoing prolonged laparoscopic procedures.

L-Arginine reduces liver and biliary tract damage after liver transplantation from non-heart-beating donor pigs

Background. To evaluate whether l-arginine reduces liver and biliary tract damage after transplantation from non heart-beating donor pigs. Methods. Twenty-five animals received an allograft from non-heart-beating donors. After 40 min of cardiac arrest, normothermic recirculation was run for 30 min. The animals were randomly treated with l-arginine (400 mg·kg−1 during normothermic recirculation) or saline (control group). Then, the animals were cooled and their livers were transplanted after 6 hr of cold ischemia. The animals were killed on the 5th day, liver damage was assessed on wedged liver biopsies by a semiquantitative analysis and by morphometric analysis of the necrotic areas, and biliary tract damage by histological examination of the explanted liver. Results. Seventeen animals survived the study period. The histological parameters assessed (sinusoidal congestion and dilatation, sinusoidal infiltration by polymorphonuclear cells and lymphocytes, endothelitis, dissociation of liver cell plates, and centrilobular necrosis) were significantly worse in the control group. The necrotic area affected 15.9±14.5% of the liver biopsies in the control group and 3.7±3.1% in the l-arginine group (P <0.05). Six of eight animal in the control group and only one of eight survivors in the l-arginine group developed ischemic cholangitis (P <0.01). l-Arginine administration was associated with higher portal blood flow (676.9±149.46 vs. 475.2±205.6 ml·min·m−2;P <0.05), higher hepatic hialuronic acid extraction at normothermic recirculation (38.8±53.7% vs. −4.2±18.2%;P <0.05) and after reperfusion (28.6±55.5% vs. −10.9±15.5%;P <0.05) and lower levels of &agr;-glutation-S-transferase at reperfusion (1325±1098% respect to baseline vs. 6488±5612%;P <0.02). Conclusions. l-Arginine administration during liver procurement from non heart beating donors prevents liver and biliary tract damage.

Postoperative Pain Relief After Hepatic Resection in Cirrhotic Patients: The Efficacy of a Single Small Dose of Ketamine Plus Morphine Epidurally

In cirrhotic patients undergoing hepatic surgery, postoperative analgesia remains a challenge. In this study, we evaluated the efficacy of a single dose of morphine combined with small-dose ketamine given epidurally for postoperative pain relief. One-hundred-four classification “Child A” cirrhotic patients were randomly assigned to two groups: 1) (MKG, n = 54): epidural morphine (3.5–5 mg) plus ketamine (20/30 mg); and 2) epidural morphine (3.5/5 mg) (MG, n = 50). The level of analgesia, side effects, psychomimetic and neurological disorders, additional analgesic needs, and overall quality of the analgesia were recorded. The mean duration of analgesia was longer in the MKG group (27.2 ± 8 h versus 16.4 ± 10 h;P < 0.05). In the MKG group, the visual analog scale (VAS) score began to be significantly lower from 14 h at rest and 12 h on coughing until the end of the study. The need for additional analgesia was also smaller in the MKG group (P < 0.05): at 24 h, only 10% of patients in the MKG group needed complementary analgesia, whereas in the MG group it was 100% (P = 0.003). Side effects were similar in both groups. Psychomimetic side effects and neurological disorders were not detected. These results suggest that postoperative analgesia provided by a single dose of epidural morphine with small-dose ketamine is effective in cirrhotic Child’s A patients having major upper abdominal surgery.

Role of dopamine in renal dysfunction during laparoscopic surgery

BackgroundSympathetic vascular insult and hemodynamic changes represent the most reliable explanation of renal impairment resulting from acute intraabdominal pressure. We evaluated the effects of low-dose dopamine administration during a long-lasting surgical laparoscopic procedure.MethodsFor this study 40, patients submitted to a colorectal laparoscopic procedure with 15 mmHg of intraabdominal pressure were randomly allocated to two groups: 20 receiving 2μg/kg/min of dopamine and 20 receiving the same perfusion of saline. Hemodynamic parameters, renal function, urinary output, and creatinine clearance, were studied.ResultsThe hemodynamic parameters were similar in both groups. The urinary output decreased during the intraoperative period only the saline group (p=0.4). Then 2 h postoperatively, it increased in both groups, and no statistically significant differences were found between the groups. The creatinine clearance decreased in both groups during the intraoperative time, but it was worse in the saline group (−28±120 vs −194±106; p=0.022). During the postoperative period, both groups showed improvement, but in control group the values remained lower than at baseline (p=0.04), and significantly lower than in the dopamine group (230±337 vs 100±192; p=0.012).ConclusionsAn intrabdominal pressure of 15 mmHg induces a time-limited renal dysfunction, and low doses of dopamine could prevent this undesirable effect.

Epidural somatostatin as an analgesic in upper abdominal surgery: a double-blind study

&NA; Somatostatin 1–14, a natural occurring neuropeptide (Somiaton®), has been reported to have analgesic effects in humans in different painful conditions. The aim of the present study was to investigate if epidural somatostatin produced clinical analgesia to postoperative pain after upper abdominal surgery. In a randomized double‐blind controlled study, 40 patients received either 125 &mgr;g of epidural somatostatin infusions every hour (using a continuous infusion pump: CADD‐PCA model 5200 PCX, Pharmacia) or placebo: mannitol (somatostatin inactif ingredient) 2.5 mg during the first 3 postoperative days (plus additional pulses of either substance, 250 &mgr;g or 5 mg, respectively, according to the level of analgesia needed by the patient). Additional subcutaneous analgesic treatment with 1 mg/kg pethidine chlorhydrate was administered at the patients request. The degree of pain was quantified with visual analogue scale at baseline, 1 h after the operation and at every 4 h for the next 3 days. Arterial blood gases and spirometry values were determined at different intervals throughout the study period. Somatostatin was significantly better than placebo for pain relief (P < 0.01) and respiratory function preservation (P < 0.05). The total consumption (and ranges) of somatostatin at 24, 48 and 72 h were: 5.2 ± 1.4 mg (4.0–6.25 mg), 4.2 ± 0.8 mg (2.2–5.0 mg) and 3.7 ± 0.4 mg (2.2–4.7 mg) respectively. During the whole study the need for complementary analgesia (pethidine chlorhydrate) was significantly higher in the placebo group: 5.4 ± 3.5 vs. 2.7 ± 1.9 (mean ± SD) P < 0.01, dose/72 h. Side effects were irrelevant and scarce in both groups. The sustained pain relief combined with the respiratory function preservation in the somatostatin group suggests an important role of this drug in postoperative analgesia.

Impact of experimental haemodilution on platelet function, thrombin generation and clot firmness: effects of different coagulation factor concentrates

BACKGROUND Haemodilution during resuscitation after massive haemorrhage may worsen the coagulopathy and perpetuate bleeding. MATERIALS AND METHODS Blood samples from healthy donors were diluted (30 and-60%) using crystalloids (saline, Ringers lactate, Plasmalyte(TM)) or colloids (6% hydroxyethylstarch [HES130/0.4], 5% human albumin, and gelatin). The effects of haemodilution on platelet adhesion (Impact R), thrombin generation (TG), and thromboelastometry (TEM) parameters were analysed as were the effects of fibrinogen, prothrombin complex concentrates (PCC), activated recombinant factor VII (FVIIa), and cryoprecipates on haemodilution. RESULTS Platelet interactions was already significantly reduced at 30% haemodilution. Platelet reactivity was not improved by addition of any of the concentrates tested. A decrease in TG and marked alterations of TEM parameters were noted at 60% haemodilution. HES130/0.4 was the expander with the most deleterious action. TG was significantly enhanced by PCC whereas rFVIIa only caused a mild acceleration of TG initiation. Fibrinogen restored the alterations of TEM parameters caused by haemodilution including those caused by HES 130/0.4. Cryoprecipitates significantly improved the alterations caused by haemodilution on TG and TEM parameters; the effects on TG disappeared after ultracentrifugation of the cryoprecipitates. DISCUSSION The haemostatic alterations caused by haemodilution are multifactorial and affect both blood cells and coagulation. In our in vitro approach, HES 130/0.4 had the most deleterious effect on haemostasis parameters. Coagulation factor concentrates did not improve platelet interactions in the Impact R, but did have favourable effects on coagulation parameters measured by TG and TEM. Fibrinogen notably improved TEM parameters without increasing thrombin generation, suggesting that this concentrate may help to preserve blood clotting abilities during haemodilution without enhancing the prothrombotic risk.

A Multicentre, Randomised, Double-Blind Study to Compare the Efficacy and Tolerability of Dexketoprofen Trometamol versus Diclofenac in the Symptomatic Treatment of Knee Osteoarthritis

AbstractBackground: Dexketoprofen trometamol (DKP.TRIS) is the tromethamine salt of dexketoprofen, the S-enantiomer responsible for the pharmacological activity of ketoprofen. DKP.TRIS has rapid absorption and onset of action in pain relief. Objective: To compare the efficacy and tolerability of DKP.TRIS and diclofenac, a nonsteroidal anti-inflammatory drug widely accepted as reference therapy for symptomatic treatment of osteoarthritis, in patients with chronic pain due to knee osteoarthritis. Design: This was a multicentre, randomised, comparative, double-blind study. Methods: Radiological evidence of osteoarthritis, shown by the presence of Kellgren grade 2 to 4 changes, was required. Patients were evaluated before and after a washout period of 7 to 14 days and after 1 and 2 weeks of treatment with DKP.TRIS 25mg three times daily orally or diclofenac 50mg three times daily orally. Primary end-points were reduction of pain measured on a visual analogue scale (VAS, 0 to 100mm) and disability measured by the Lequesne index of severity for knee osteoarthritis (ISK). Tolerability was evaluated by laboratory parameters and frequency and nature of adverse events. Results: Of 117 patients recruited to the study, 115 were treated (61 with DKP.TRIS, 54 with diclofenac) and 99 (54/45) completed the 2-week treatment period. Patient characteristics were homogenous between groups. Pain measured on the VAS decreased by 43% from 61.7 ± 18.5mm (mean ± SD) at baseline to 34.7 ± 22.3mm at the end of treatment with DKP.TRIS compared with a 29% decrease from 62.1 ± 22.7mm to 40.6 ± 22.2mm for diclofenac [p = 0.027; 95% confidence interval (CI) for the difference between treatments: 1.7, 27.9]. Median ISK scores improved from 11 (range 9 to 12) to 8 (6 to 10) in the DKP.TRIS group versus 10.75 (9 to 12.5) to 8.5 (6 to 10.5) in the diclofenac group. There were no group differences for secondary end-points. Adverse events were comparable overall between groups. Conclusion: Oral DKP.TRIS 25mg three times daily is at least as effective as diclofenac 50mg three times daily for the short term treatment of pain in patients with osteoarthritis of the knee.