Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine.

BACKGROUND: Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD NasalTM). METHODS: This prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 µg kg-1 dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM. RESULTS: The i.v. route had a significantly faster onset (15 min, 95% CI 15-20 min) compared to intranasal routes by atomiser (47.5 min, 95% CI 25-135 min), and by drops (60 min, 95%CI 30-75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7-54.4%) and 40.7% (95% CI 36.5-53.2%) for atomisation and drops respectively. Sedation score was modelled via a sigmoidal Emax model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8-4.7) min-1, and the EC50 was estimated to be 903 (95% CI 450-2344) pg ml-1. CONCLUSIONS: There is no difference in bioavailability with atomisation or nasal drops. A similar degree of sedation can be achieved by either method. CLINICAL TRIAL REGISTRATION: HKUCTR-1617.

Intrarenal abscess caused by community-associated methicillin-resistant Staphylococcus aureus in a transplanted kidney.

Emergence of multidrug-resistant bacteria is important in solid organ transplant recipients, because it can jeopardize patient and graft survival. Methicillin-resistant Staphylococcus aureus (MRSA) infections are not rare in kidney transplant recipients. On the other hand, infections related to community-associated MRSA (CA-MRSA) strains are seldom reported in the literature. Herein, we report the first patient, to our knowledge, with CA-MRSA renal graft abscess who was successfully treated with drainage and parenteral antibiotics.

The short-to-midterm results of endovascular stent grafting for acute thoracic aortic diseases in Chinese patients.

OBJECTIVE: To review the results of endovascular treatment of acute thoracic aortic diseases in a group of Chinese patients. DESIGN: Retrospective study. SETTING: A tertiary referral hospital with a cardiothoracic surgery service. PATIENTS: All 15 patients presenting with acute thoracic aortic diseases between September 2001 and October 2005 inclusive, of whom eight had traumatic rupture, four had complicated acute dissections, two had mycotic aneurysms, and one an aneurysm with an aortobronchial fistula. INTERVENTIONS: Thoracic aortic stent grafting. MAIN OUTCOME MEASURES: Immediate success, 6-month and 1-year survival rates. RESULTS: The median follow-up period was 20.6 months (range, 0-50.1 months). Stent grafts were deployed with immediate success in all patients. Two patients had ancillary bypass surgery for the supra-aortic branches. There were two in-hospital deaths. Four sustained access artery injury and needed graft repair. Computed tomography at 1 month showed complete thrombosis of the aneurysmal lumen or the thoracic aortic false lumen in 12 of 13 survivors. Computed tomography at 6 months showed complete thrombosis of the aneurysmal lumen or the false lumen in nine of 10 patients due for follow-up. Both 6-month and 1-year survival rates were 87%. CONCLUSIONS: Thoracic aortic stent grafting for acute thoracic aortic disease is feasible and has a high success rate, with good short-to-midterm results. However, the large size of the stent graft introducer set imposes a high risk of access artery injury, for which further improvements are necessary.

Uterine fibroid embolisation in Chinese women: medium-term results.

OBJECTIVE: To evaluate the medium-term results of uterine fibroid embolisation in Chinese women with symptomatic uterine fibroids. DESIGN: Prospective case series study. SETTING: Gynaecology and Interventional Radiology units in a public hospital, Hong Kong. PATIENTS: Patients with symptomatic fibroids who underwent uterine fibroid embolisation in Queen Elizabeth Hospital from October 1998 to June 2004. RESULTS: Fifty women (mean age, 42.9 years; median follow-up period, 27.5 months) were recruited. Most (82%) had menorrhagia as the chief presenting symptom. Embolisation was successful in 49 (98%) women. Complications occurred in 12 (24%) patients, but were all self-limiting. Significant decrease in the median clinical uterine size (14 weeks vs 10 weeks) and median volume of the largest fibroid on magnetic resonance imaging (157.9 mL vs 45 mL) were observed during the first year. The reduction seemed to be maintained till the last follow-up. Menorrhagia improved in 34 (84%) patients, dysmenorrhoea in 28 (88%), pelvic pain in 18 (82%) and abdominal mass in 15 (83%). Poor response was found for urinary symptoms (29% improvement). Eight (16%) patients underwent hysterectomies after uterine fibroid embolisation. On logistic regression analysis, the only significant predictive factor for symptomatic improvement was fibroid volume reduction at 6 months (P=0.03). CONCLUSION: Uterine fibroid embolisation is an effective uterine-preserving therapy in patients with symptomatic fibroids; overall symptomatic improvement was estimated as 80%. Uterine or fibroid size reduction correlated well with clinical outcome. The impact of uterine fibroid embolisation on young women wishing to conceive is yet to be determined.

Pneumonia and mesenteric lymphadenopathy caused by disseminated Penicillium marneffei infection in a cadaveric renal transplant recipient.

A38-year-old cadaveric kidney transplant recipient presented with fever, pneumonia, and mesenteric lymphadenopathy 9 months after transplant. Blood culture, bone marrow culture, and fine-needle aspiration cytology of mesenteric lymph nodes confirmed the diagnosis of disseminated Penicillium marneffei infection. He recovered after receiving parenteral amphotericin B followed by oral itraconazole therapy. P. marneffei infection is a dimorphic fungal opportunistic infection endemic in Southeast Asia, southern China, Taiwan, and Hong Kong. It has been well reported in human immunodeficiency virus (HIV)-positive patients in the endemic areas, and also in other immunocompromised patients. This diagnosis must be considered for all febrile transplant recipients who have the relevant clinical features and travel history to Southeast Asia. Prompt treatment with anti-fungal therapy improves the survival and outcome of these patients.

Emergency aortic stent grafting for traumatic rupture of the thoracic aorta.

OBJECTIVE: To investigate the role of aortic stent grafting in emergency treatment of traumatic rupture of the descending thoracic aorta in patients with multiple injuries. DESIGN: Retrospective study. SETTING: Cardiothoracic surgery facility of a tertiary referral hospital, Hong Kong. PATIENTS: Between September 2001 and September 2002, four patients who had sustained a blunt injury to the chest after high-speed deceleration injury were recruited. Three patients were treated with stent grafting because concomitant head injury and multiple other injuries precluded the use of open thoracic surgery. One patient had no head injury and was offered stent grafting as a less invasive treatment. INTERVENTION: The pseudoaneurysm was covered with an aortic stent graft under fluoroscopic and angiographic guidance. MAIN OUTCOME MEASURES: Technical success of treatment, complications, and treatment outcome. RESULTS: Three patients recovered and were discharged from hospital. The computed tomography scan at 3 months to 6 months after surgery showed resolution of the pseudoaneurysm. The final patient was still in the hospital. Follow-up computed tomography 2 weeks later showed exclusion of the pseudoaneurysm. There was one external iliac artery thrombosis on the side of femoral arteriotomy, which was recanalised with thrombectomy. There was another unintentional partial coverage of the left subclavian artery, which was asymptomatic. No other major complication was present and there was no paraplegia after the stent grafting. CONCLUSION: Aortic stent graft is useful for emergency treatment of descending thoracic aortic injury. In the short term, it causes less morbidity and mortality than does open surgery, and can be life-saving when there is no surgical alternative. The long-term effect is still unknown.

Rare pulmonary complications after transarterial chemoembolisation for hepatocellular carcinoma: two case reports.

We report two rare cases of acute pulmonary complication after transarterial chemoembolisation for inoperable hepatocellular carcinoma. Both cases involved a large tumour and hepatic vein invasion. The first patient, a 27-year-old man, died of pulmonary tumour embolism 4 days after transarterial chemoembolisation. Acute dyspnoea developed in the second patient, a 63-year-old man, following the procedure due to pulmonary oil embolisation and chemical pneumonitis. The chest condition of this patient improved, but he subsequently died of liver failure 3 weeks later. Our cases illustrate the point that if locoregional treatment is offered as a palliative treatment, patients with hepatic vein invasion should be warned of the possible complications of massive tumour embolism, pulmonary oil embolisation, and subsequent death.

Percutaneous transhepatic choledochoscopic removal of intrahepatic stones.

BACKGROUND: Treatment of hepatolithiasis is complex and difficult. With the advent of biliary endoscopy and radiological intervention, percutaneous choledochoscopic removal of intrahepatic stones has become a well established procedure. METHODS: Seventy-nine patients with intrahepatic stones that were removed by percutaneous transhepatic choledochoscopy (PTCS) between 1993 and 2001 were studied retrospectively. The results of the procedure and the long-term outcome of these patients were analysed. RESULTS: The success rate of choledochoscopic removal of intrahepatic stones was 76.8 per cent. Complications occurred in 17 patients (21.5 per cent). Removal of stones predominantly on the right side was difficult using this method. Cholangitis occurred in about one third of patients within 3-5 years after PTCS. For patients with a stricture, cholangitis recurred gradually over the years of follow-up. CONCLUSION: Intrahepatic stricture was the major determinant for the recurrence of stones or symptoms. Hepatic resection should be offered to these patients if the disease is localized in one liver segment or lobe. In other cases, percutaneous choledochoscopy and stricture dilatation is a useful solution, and may reduce further damage to the liver.

Neurologic injury after endovascular stent-graft and bilateral internal iliac artery embolization for infrarenal abdominal aortic aneurysm.

The authors report a rare neurologic complication after the implantation of a bifurcated stent-graft for abdominal aortic aneurysm. The stent-graft was extended to both external iliac arteries after embolization of both internal iliac arteries. The patient subsequently had weakness and numbness of both lower limbs with bowel and bladder incontinence. He probably had ischemic injury to the nerve roots or the lumbosacral plexus, which was related to extensive occlusion of their supplying arteries. The mechanism of spinal cord and neurologic ischemia after aortic stent-graft implantation is discussed.

Prevention of recurrent central venous stenosis using endovascular irradiation following stent placement in hemodialysis patients.

This study was done to evaluate the outcome after brachytherapy (BT) given to prevent restenosis after stent insertion for central venous stenosis in patients with ipsilateral hemodialysis arteriovenous fistulas (AVF). Angioplasty and stenting were performed on 9 primary central venous stenoses in 8 patients with AVF followed by BT, delivering Iridium-192 radiation using an afterloading technique. BT was also administered to three patients with five recurrent stenoses at the stent margins. There was no residual stenosis after angioplasty and stenting. Venographic follow-up (77-644 days, mean 272 days) showed no restenosis in seven primary stenoses. New strictures (45%-100%) developed at the stent margin in six veins (five patients). Angioplasty or stenting was performed for five margin stenoses in three patients, followed by a second BT. Residual stenosis before BT was 0-30%. In our venographic follow-up (140-329 days, mean 215 days), three restenoses occurred (35%-100%). All progressed to complete occlusion on later venographic follow-up irrespective of whether BT was given to the stent margin or not. The mean primary and assisted primary patency of the central veins were 359 days and 639 days, respectively. Endovascular irradiation with a noncentering source does not prolong the patency after angioplasty and stenting of central venous stenosis in hemodialysis patients.

A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma.

BACKGROUND/AIM: Inoperable hepatocellular carcinoma is common in Asia and is usually treated with repeated transarterial chemoembolization. Gunji et al. showed better survival and fewer complications with autologous blood clot as compared with gelfoam used for embolization. Our aim was to compare the effect of blood clot versus gelfoam. METHODS: We conducted a prospective randomized trial in 100 patients with inoperable hepatocellular carcinoma, and compared the side effects and cumulative survival in the two groups. Cox's proportional hazard model was used to study the prognostic factors. RESULTS: The diameter of the main tumor was 7.9+/-4.6 cm. Our study did not show additional beneficial effects of blood clot. The proportion of side effects was similar and the common ones included fever, pain and vomiting. Though the hepatic artery remained patent for a longer period with blood clot (p=0.061), there was no difference in survival (p=0.129 for Okuda I disease and p=0.388 for Okuda II disease). Subgroup analysis showed longer survival in patients with vascular occlusion (p=0.034 for Okuda I and p=0.029 for Okuda II disease). The independent factors of survival were sex, Child's class, Okuda stage, tumor type and presence of metastases. CONCLUSION: This study showed no additional benefits of blood clot in patients with inoperable hepatocellular carcinoma, in Okuda I and II disease. The longer survival in patients with vascular occlusion suggested that the damage to normal liver tissue by planned periodic transarterial chemoembolization may outweigh its benefit in later sessions of repeated TACE in certain patients.

Percutaneous ethanol injection as a possible curative treatment for malignant portal vein thrombosis in hepatocellular carcinoma.

Postoperative residual hepatocellular carcinoma (HCC) with malignant portal vein thrombosis in a 48-year-old man was cured with transarterial chemoembolization (TACE) for the parenchymal portion and percutaneous ethanol injection (PEI) for the malignant portal vein thrombosis. No evidence of tumor recurrence was noted after 18 months of follow-up. The only severe complication in our patient was biliary stricture which was treated with an internal stent via endoscopic retrograde pancreatico-cholangiography (ERCP).

A radiological approach to the through and through technique for percutaneous passage of ureteric strictures.

Some ureteric strictures are so tight that they are difficult to traverse with balloon catheters or internal stents. We present five such cases, which were traversed using a modified through and through technique with a hydrophilic coated guide-wire. The reasons for the difficulty are discussed, and the merits of the modified technique compared with conventional techniques are described.

A blinded clinical trial comparing conventional cleansing enema, Pico-salax and Golytely for barium enema bowel preparation.

UNLABELLED: An evaluator-blinded randomized clinical trial was undertaken to assess the effectiveness and patient acceptance of three bowel cleansing regimens: conventional cleansing enema, Pico-salax and Golytely. PATIENTS AND METHODS: One hundred and fifty patients, referred for barium enema examination, were allocated to one of the three regimens. Both the radiographers and the radiologists did not know the method of preparation. Radiographers were requested to enter the patients' data, the number of bowel openings, the patients' comments of the preparation and side effects. Films were reviewed independently by two experienced radiologists for the degree of bowel cleanliness and quality of barium coating. RESULTS: The mean (standard deviation) of bowel opening frequency for the cleansing enema, Pico-Salax and Golytely were 3.6(4.4), 8.3(4.8) and 7.1(4.2), respectively, with less bowel opening in the cleansing enema. There was less nausea associated with the cleansing enema (P = 0.006), more vomiting with Golytely (P = 0.008), less abdominal fullness with Pico-salax (P = 0.0006), less anorectal irritation with Golytely (P = 0.025), and no difference in the abdominal pain amongst three groups. There was no statistically significant difference in the number of bowel openings between the groups. Patients found that Pico-salax tasted better than Golytely (P = 0.0094) and Golytely was less accepted in the amount of fluid intake (P = 0.0018 and P < 0.0002 comparing Golytely with the cleansing enema and Pico-salax). Chi-squared testing showed no statistically significant difference in bowel cleanliness and quality of barium coating among the three preparations. CONCLUSIONS: There was no difference in the effectiveness of the three regimens. Pico-salax seems the most acceptable because it has the fewest side effects.