Prolonged use of high-dose morphine impairs angiogenesis and mobilization of endothelial progenitor cells in mice.

BACKGROUND: Morphine is one of the most commonly prescribed analgesics for treating wound pain. Using a mouse model of excisional wound injury, we determined the effects of high-dose morphine on angiogenesis and mobilization of endothelial progenitor cells. METHODS: An excisional wound was created on mice treated with placebo or morphine (20 mg/kg, i.p. injection for 14 days). Wound healing was compared by measuring the final-to-initial wound area ratio. Generation of superoxide anions in the wound was determined by luminol-enhanced chemiluminescence. Circulating mononuclear cells were isolated and measured for endothelial progenitor cell (defined as CD34+/CD133+ cell) counts. In vivo and in vitro measurements of angiogenesis after morphine treatment were performed using the Matrigel assay. RESULTS: Mice treated with morphine had reduced wound closure and higher wound superoxide ions concentrations than control mice. Morphine reduced the number of postwound circulating endothelial progenitor cells. Matrigel assay showed impaired angiogenesis in animals and reduced capillary tube formation in cultured endothelial cells treated with morphine. CONCLUSION: High-dose morphine impaired angiogenesis, increased systemic oxidative stress, and impaired mobilization of endothelial progenitor cells. This study emphasizes the potential detrimental effect of high-dose morphine on angiogenesis after systemic administration.

Continuous cerebrospinal fluid drainage using a lumbar subarachnoid catheter for cerebrospinal fluid rhinorrhea after functional endoscopic sinus surgery.

Anesthesiologists are frequently consulted for performing lumbar cerebrospinal fluid (CSF) drainage to facilitate surgery or manage complications. Functional endoscopic sinus surgery (FESS) is a common treatment for chronic sinus diseases. Cerebrospinal fluid (CSF) leakage is a serious complication following FESS and is typically treated with an endonasal free or rotational mucoperichondrial flap. Continuous drainage of CSF with a lumbar subarachnoid catheter has been used in patients who have undergone neurosurgery but it is seldom used in the treatment of post-FESS CSF rhinorrhea. We present a 71-year-old male patient who suffered from CSF rhinorrhea after FESS, and was treated successfully with continuous lumbar CSF drainage. We are of the opinion that continuous CSF drainage with a lumbar subarachnoid catheter is an effective and safe modality of treatment for post-FESS CSF leakage.

High-dose morphine impairs vascular endothelial function by increased production of superoxide anions.

BACKGROUND: The effects of high-dose morphine on vascular endothelial function have not been previously shown. The authors hypothesized that the pro-oxidant effect of high-dose morphine impairs vascular endothelial function. METHODS: Mice were subjected to placebo or morphine (20 mg/kg intraperitoneal) injection for consecutive 14 days. Aortas were harvested for assessment of vasomotor function by isometric force recordings. Protein expression p47phox was determined by Western blotting. Generations of superoxide anions were detected under a confocal microscope. RESULTS: Compared with controls, contraction response to phenylephrine was significantly enhanced in the aorta of mice treated with high-dose morphine (maximal contractions were 150 +/- 26 vs. 261 +/- 32 mg, respectively; n = 5 or 6, P = 0.04). Endothelium-dependent relaxations to acetylcholine (10 to 10 m) were significantly reduced in morphine-treated animals but were normalized by superoxide scavenging. Fluorescent densities of dihydroethidium were increased in the aorta of morphine-treated mice. Aorta of mice treated with morphine expressed higher levels of p47phox (a major subunit of nicotinamide adenine dinucleotide phosphate oxidase). In cultured endothelial cells, morphine enhanced production of reactive oxygen species. CONCLUSIONS: Collectively, the authors' results showed that high-dose morphine impairs vascular endothelial function via attenuation of biologic activity of endothelium-derived nitric oxide. Chemical antagonism between superoxide anions generated by nicotinamide adenine dinucleotide phosphate oxidases may be the molecular mechanism responsible for the inactivation of endogenous nitric oxide after treatment with high-dose morphine.

Severe bronchospasm during laryngeal mask airway placement in an infant.

A 35-day-old male infant was scheduled for bilateral inguinal herniorrhaphy. No history of recent upper airway infection or other reactive respiratory disease was noted before anesthesia. Breath holding was noted immediately after laryngeal mask airway (LMA) insertion. Removal of the LMA and positive pressure ventilation via face mask did not solve the problem. On suspicion of laryngospasm, tracheal intubation facilitated by muscule relaxant was performed. However, when the patient was ventilated, high airway pressure, absence of chest wall movement and elevated end-tidal CO2 were noted. Despite visual confirmation of correct placement of tracheal tube, oxygen desaturation and bradycardia developed rapidly. After deepening the inhalational anesthesia of sevoflurane and concomitant administration of intravenous lidocaine, the patient's respiratory condition turned for the better and became compliable. Respiratory dysfunction may be caused by severe bronchospasm induced by placement of the LMA. The pathophysiology and risk factors of bronchospasm related to the LMA placement are discussed in the text.