Assessment of delta-9-tetrahydrocannabinol (THC) in saliva and blood after oral administration of medical cannabis with respect to its effect on driving abilities.

Medical cannabis has recently been legalized in many countries, and it is currently prescribed with increasing frequency, particularly for treatment of chronic pain resistant to conventional therapy. The psychoactive substance delta-9-tetrahydro-cannabinol (THC) contained in cannabis may affect driving abilities. Therefore, the aims of this study (open-label, monocentric, nonrandomized) were to evaluate blood and saliva concentrations of THC after oral administration of medical cannabis and to assess the time needed for THC levels to decline below a value ensuring legal driving. The study involved 20 patients with documented chronic pain using long-term medical cannabis therapy. They were divided into two groups and treated with two different doses of cannabis in the form of gelatin capsules (62.5 mg or 125 mg). In all patients, the amount of THC was assessed in saliva and in blood at pre-defined time intervals before and after administration. THC levels in saliva were detected at zero in all subjects following administration of both doses at all-time intervals after administration. Assessment of THC levels in blood, however, showed positive findings in one subject 9 h after administration of the lower dose and in one patient who had been given a higher dose 7 h after administration. Our finding suggested that for an unaffected ability to drive, at least 9-10 h should elapse from the last cannabis use.

[Systematic mediastinal lymphadenectomy in surgery for sarcomatous pulmonary metastases]. / Význam systematické mediastinální lymfadenektomie v chirurgii plicních metastáz sarkomového puvodu.

PURPOSE OF THE STUDY: Systematic lymph node dissection is performed as standard curative resection for non-small cell lung cancer. Its role in lung metastasectomy is unknown. The aim of our study was to find out the frequency of lymph node metastases, the survival of patients with and without lymph node involvement, and to consider if routine lymph node dissection should be recommended. MATERIAL AND METHODS: The study was undertaken at three departments of surgery and included 14 patients undergoing lung metastasectomy between July 2008 and December 2011. In all patients systematic lymph node dissection was also performed. When wedge resection was done, N1 nodes were removed only as part of a local procedure at that anatomical site. Patients with mediastinal lymph node involvement detected by pre-operative CT or PET scans were not included in the study. RESULTS: Lung metastasectomy for metastatic sarcoma was performed in 14 patients. Nine patients had bilateral lung metastases. Solitary lung metastasis was found in only one case. The mean number of removed mediastinal lymph nodes was 14.8 (7-32). Mediastinal lymph node metastases were found in two patients (14.3%). The average disease free interval (DFI) was 79.6 months (median, 25.5 months). Using the Kaplan-Meier method, the 3-year survival rate was 46% (0.46±0.15). The Cox-Mantel test for comparing the survival curves showed, at a 0.05 level of significance, better survival rates for the patients with no metastatic lymph node involvement (p=0.01). DISCUSSION: The frequency of mediastinal lymph node involvement in our study was 14.3% and this was in agreement with the data reported in the literature. The 3-year survival rate was 46% in our patients; the published 5-year survival is 15-50%. A systematic mediastinal lymphadenectomy during lung metastasectomy for metastatic sarcoma has been recommended, but also argued against because of a low incidence of mediastinal lymph node involvement in sarcomatous metastases reported by some authors. We showed that mediastinal lymph node involvement was a negative prognostic factor. Systematic mediastinal lymphadenectomy as a routine procedure provides for a better staging. This is important in association with the development of adjuvant modalities, such as monoclonal antibodies, at present or a gene therapy in the future. CONCLUSIONS: Even in a carefully selected group of patients, incidence of mediastinal lymph node metastases is high. Since no relevant data based on large patient groups are available, we recommend routine nodal dissection for all patients indicated for lung metastasectomy. Drawing a definite conclusion will require analyses of large numbers of data from multi-institutional studies and cooperation with the international database, if possible.

Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR).

PURPOSE: Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. METHODS: In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. RESULTS: The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5-1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50 %) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p = 0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r = 0.79; p < 0.001). CONCLUSION: The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.

Porcine model of ruptured abdominal aortic aneurysm repair.

OBJECTIVES: To validate a porcine model of ruptured abdominal aortic aneurysm (rAAA) repair. DESIGN: Experimental study. METHODS: Ten experimental and five sham-operated pigs were studied. Instrumentation for cardiac output (CO) measurement, regional blood flow (renal-REN and portal-PORT) and blood sampling (inferior vena cava (IVC), renal and portal vein) was done. Microcirculation was visualised sublingually and in ileostoma. PROTOCOL: simulation of rAAA with bleeding (mean arterial pressure (MAP) 45 mmHg) and increased abdominal pressure (25 mmHg) for 4 h; 2 h of infrarenal clamp with shed blood retransfusion; 11 h of post-surgery care. RESULTS: Six experimental pigs completed the protocol and are presented. Bleeding decreased CO to 95%, PORT to 80% and REN to 10% of baseline. From clamping on CO and PORT increased above baseline whereas REN (47%) with creatinine clearance remained compromised till the end. Microcirculation was affected more in ileum than sublingually. Approximately threefold increase in cytokines (tumour necrosis factor-α (TNF-alpha), interleukin (IL)-6 and IL-10) and oxidative stress markers (thiobarbituric acid-reactive substances (TBARs) and 4-hydroxy-2-trans-nonenal (HNE) was observed. Only mild increase in IL-6 and TBARs was observed in sham-operated animals. Organ histology did not reveal differences between groups. CONCLUSIONS: This near-lethal model of rAAA induced expected severe deterioration of haemodynamics and metabolism accompanied with a moderate inflammatory and oxidative stress response.

Respiratory induced heart rate and blood pressure variability during mechanical ventilation in critically ill and brain death patients.

UNLABELLED: We analysed respiratory induced heart rate and blood pressure variability in mechanically ventilated patients with different levels of sedation and central nervous system activity. Our aim was to determine whether it is possible to distinguish different levels of sedation or human brain activity from heart rate and blood pressure. We measured 19 critically ill and 15 brain death patients ventilated at various respiratory frequencies - 15, 12, 8 and 6 breaths per minute. Basal and deeper sedation was performed in the critically ill patients. We detected and analysed heart rate and blood pressure parameters induced by ventilation. RESULTS: Respiratory induced heart rate variability is the unique parameter that can differentiate between brain death patients and sedated critically ill patients. Significant differences exist, especially during slow deep breathing with a mean period of 10 seconds. The limit values reflecting brain death are: baroreflex lower than 0.5 ms/mmHg and tidal volume normalised heart rate variability lower than 0.5 ms/ml. Reduced heart rate variability parameters of brain death patients remain unchanged even after normalisation to respiration volume. However, differences between basal and deep sedation do not appear significant on any parameter.

[Rates of metastatic affections of mediastinal nodes during pulmonary metastasectomy]. / Cetnost metatastického postizení mediastinálních uzlin behem plicní metastasektomie.

OBJECT: The aim is the evaluation of lymph node metastasis rate during pulmonary metastasectomy harvested by technique of systematic mediastinal lymphadenectomy in year 2009-2010. METHODS: We performed systematic mediastinal lymphadenectomy (the same technique as in non-small cell lung cancer) during pulmonary metastasectomy. RESULTS: There was found lymph node metastasis in four cases from 70 patients. The rate of metastatic involved mediastinal lymph node 5.7% harvested during lung metastasectomy is on lower limit of published interval. We expected higher lymph node involvement in lung metastasis of colorectal origin.

Rare incidence of pulmonary gangrene--algorithm of the treatment.

The pulmonary gangrene is rare and serious disease. Our experience is based on the treatment of the 2 patients with pulmonary gangrene during the last twenty years. The first and lifesaving step in the treatment of sepsis is the early removal of the necrotic tissue. Next surgery succeeds usually after one week after initial treatment. Surgical treatment continues step by step, we do not advise providing of a major anatomical resection in the initial stage of the disease. This policy is effective in the treatment of this serious disease.

The improvement of arterial oxygenation during one-lung ventilation--effect of different CPAP levels.

Authors studied different continuous positive airway pressure (CPAP) levels and their effect on arterial oxygenation during thoracic surgery. Surgical interference of CPAP was studied as well. No significant difference has been found at 4 cm, 7 cm and 10 cm H2O in the improvement of oxygen content during one-lung ventilation. In contract to the lowest CPAP level, 7 cm and 10 cm H2O made the surgical conditions significantly worse.