Does N-acetylcysteine increase the excretion of trace metals (calcium, magnesium, iron, zinc and copper) when given orally?

N-Acetylcysteine (NAC) is known to decrease the exacerbation rate in patients with chronic bronchitis. It has also been shown that NAC has both an oxygen-radical scavenger and a heavy-metal chelating effect in high intravenous doses. In a study lasting 5 weeks, 10 healthy volunteers were treated with NAC 200 mg t.d.s. for two weeks. The concentrations of trace metals (Ca, Mg, Fe, Zn & Cu) in plasma were measured weekly and daily in a morning spot urine during the investigation. No significant change in plasma concentration or excretion was found during the two weeks of treatment, implying that additional administration of trace metals is unnecessary for patients treated perorally with a therapeutic dose of NAC.

Pain relief following herniotomy: a double-blind randomized comparison between naproxen and placebo.

Sixty consecutive out-patients were randomly assigned to have either a non-steroid anti-inflammatory drug (naproxen 500 mg) or an identical placebo administered as suppositories half an hour before unilateral herniotomy. Within 1.5 h after the end of surgery, pain scores were significantly improved in patients receiving naproxen (P less than 0.02). The long-term analgesic effect was measured indirectly by registering the postoperative requirement for supplementary analgesic doses of acetylsalicylic acid 1 g plus codeine 20 mg. The time elapsing before the first demand for additional analgesics was prolonged by median 1.5 h, and the need for further analgesic treatment during 24 h was significantly reduced (P less than 0.003) in the naproxen group (median, 2 doses) compared to the placebo group (median, 4 doses). No statistically significant difference was found between the groups with regard to the occurrence of side-effects.

Influence of combined neural blockade, H1- and H2-receptor and serotonin2-receptor blockade, indomethacin and tranexamic acid on leucocyte, temperature and acute-phase protein response to surgery.

Body temperature, P-cortisol, P-glucose, P-transferrin, P-orosomucoid, P-IgM, hematocrit and total and differential leucocyte counts were investigated in 16 men undergoing inguinal herniotomy. The patients were randomized to epidural analgesia (n = 8) or epidural analgesia + assumed blockade of prostaglandin synthesis, blockade of receptors for histamine1, histamine2 and serotonin2, and inhibition of fibrinolysis with indomethacin, astemizole, ranitidine, ketanserin and tranexamic acid, respectively (n = 8). The rectal temperature and blood granulocyte counts rose significantly and similarly after surgery in both groups. Acute-phase protein (transferrin and orosomucoid) changes were also similar in both groups, as were P-cortisol and P-glucose, which did not increase in response to the neural blockade. Other factors than neural stimuli, prostaglandins, histamine, serotonin and activation of fibrinolysis are concluded to be effective in releasing postoperative leucocytosis, rise in body temperature and changes in acute-phase proteins.

ARDS after accidental inhalation of zinc chloride smoke.

Five soldiers were injured by inhalation of hexite smoke (ZnCl2) during military training. Two soldiers, not wearing gas masks breathed hexite for 1 or 2 min, they slowly developed severe adult respiratory distress syndrome (ARDS) over the ensuing 2 weeks. This slow, progressive clinical course has not been previously described. In both patients, an increased plasma zinc concentration was measured 3 weeks after the incident. Intravenous and nebulized acetylcysteine increased the urinary excretion of zinc, and briefly decreased the plasma levels. In an attempt to arrest collagen deposition in the lungs, L-3,4 dehydroproline was administered. Both patients died of severe respiratory failure (25 and 32 days after inhalation). At autopsy diffuse microvascular obliteration, widespread occlusion of the pulmonary arteries and extensive interstitial and intra-alveolar fibrosis was observed. Three soldiers wearing ill fitting gas masks, immediately developed severe coughing and dyspnea. They improved, and 12 months after exposure their lung function tests were nearly normal, but they still had slight dyspnea on exercise.

Increased hepatic microsomal activity after halothane anaesthesia in children.

The effect of anaesthesia and surgery on microsomal enzyme activity was studied in 19 children aged 4-9 years, scheduled for tonsillectomy. The children were randomly allocated to either halothane or ketamine anaesthesia. Antipyrine clearance was measured before and 4 days after surgery by a salivary one-sample technique. Statistically significant (p less than 0.001) increases in antipyrine clearance was found in children who received halothane anaesthesia. The antipyrine clearance was increased by a mean of 26% 4 days after surgery, compared with a pre-operative control measurement. No significant change in antipyrine clearance was observed in children who received ketamine anaesthesia. There was also a significant difference in antipyrine clearance changes after surgery between the two groups (p less than 0.05). Halothane has enzyme-inducing properties after a single exposure in children, while a single dose of ketamine does not.

The modifying effect of spinal anaesthesia on intra- and postoperative adrenocortical and hyperglycaemic response to surgery.

Plasma cortisol and glucose were measured in 24 patients undergoing abdominal hysterectomy during spinal anaesthesia with 0.5% hyperbaric tetracaine or neurolept anaesthesia. The sensory level of analgesia to pinprick extended to at least T4 before skin incision in the spinal group. The mean sensory analgesic level regressed almost linearly, reaching the fourth lumbar segment 4 h after incision. Plasma cortisol and glucose measurements from before to 9 h after skin incision showed significant increases in both parameters during and after surgery. Plasma cortisol and glucose levels were significantly lower during and immediately after surgery in the spinal group, but later postoperatively the mean levels were similar in the two groups. The increase in plasma cortisol 1 h after skin incision in the spinal group correlated to the segmental level of analgesia at that time (r = 0.77, P less than 0.01) and a similar correlation was found with regard to plasma glucose changes (r = 0.60, P less than 0.05). The regression lines showed that maintenance of a sensory analgesic level about the fourth thoracic segment prevented the adrenocortical and hyperglycaemic response to surgery. These findings are in accordance with the anatomical assumption that the upper segmental level of visceral afferent input to the spinal cord is about the fourth thoracic segment. Our results further demonstrate that the inhibitory effect of spinal anaesthesia on the stress response to surgery is transient, and correlates to the regression of sensory analgesia.

Epidural morphine for postoperative pain relief.

In a clinical, double-blind study including 45 patients, who all underwent lower abdominal or urological surgery, the analgesic effect, latency and duration of epidural application of morphine were investigated in doses of 2 and 4 mg, respectively, compared to placebo. No significant difference was found in the effect of 2 mg morphine, compared to placebo. A significant decrease in pain score was found in the group of patients who received 4 mg morphine administered epidurally; however, this effect did not occur until 60 min after epidural administration. The effect of 4 mg morphine was found to be of long duration, as eight out of 15 patients did not require any supplementary analgesics within the first 24 h, compared to two out of 14 and three out of 15 patients, respectively, in the placebo and 2-mg groups.

Does oral premedication increase the risk of gastric aspiration? A study to compare the effect of diazepam given orally and intramuscularly on the volume and acidity of gastric aspirate.

In a clinical study including 40 patients, who all underwent elective gynaecological surgery, the quantity and acidity of the gastric contents were compared for patients premedicated with diazepam (Apozepam) intramuscularly and orally, respectively. A significant difference was found with regard to both the quantity and acidity of the gastric fluid. The volume of gastric fluid was smaller after oral than after intramuscular premedication with diazepam (1.5 ml and 20 ml, respectively). The acidity of the gastric fluid was also less after oral than after intramuscular premedication (pH 2.4 and 1.8, respectively).