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Acute overdose of levothyroxine in a dog.

An overdose of up to 850 levothyroxine sodium tablets (0.2 mg) in a healthy 6-year-old 16.8-kg dog induced an episode of vomiting and hippus within 9 hours of ingestion. The dog was treated with activated charcoal and saline (magnesium sulfate) cathartic. Initially the serum concentration of thyroxine (T4) 4,900.9 nmol/L. On the second day, serum concentration of triiodothyronine (T3) was 5.3 nmol/L. Serum T4 concentration decreased slowly and was not determined to be normal until day 36. Serum T3 concentration was found to be normal on day 6. Serum alanine transaminase activity peaked on day 6 at 345 U/L. Significant abnormalities were not found during the following 36 days. Clinical signs of thyroid hormone toxicosis in dogs and cats include hyperactivity, lethargy, tachycardia, tachypnea, dyspnea, abnormal pupillary light reflexes, vomiting, and diarrhea. High overdoses of levothyroxine sodium in dogs should be managed by initial decontamination and administration of activated charcoal with a cathartic followed by supportive care.

Animals↗

[Sepsis following transrectal prostate biopsy: a report of 2 cases and reviewed similar cases in Japan].

We report two cases of sepsis and disseminated intravascular coagulation (DIC), potentially fatal complications, following transrectal prostate biopsy. We also review similar cases reported in Japan. Case 1: A 63-year-old man received a cathartic and levofloxacin (LVFX) for prophylaxis. After transrectal prostate biopsy, he presented with fever and chills. Blood cultures grew Escherichia coli resistant to LVFX. Under a diagnosis of sepsis, he received intensive management that included endotoxin removal therapy. The patient was hospitalized for 27 days. Case 2: A 64-year-old man received a cathartic and cefazolin (CEZ) for prophylaxis. He presented with fever and chills after biopsy, and was admitted to hospital. Blood cultures grew E. coli resistant to CEZ. Under a diagnosis of sepsis, he received intravenous antibiotics, transfusion, and anti-DIC drugs. The patient was hospitalized for 11 days.

Biopsy↗

Acute digoxin poisonings: review of therapy.

Acute digoxin poisoning, its recognition and management, are reviewed. The uses of syrup of ipecac, gastric lavage, activated charcoal, cholestyramine, colestipol, edetate sodium and cathartics as measures to terminate the drug exposure are discussed. Measures to hasten digoxin elimination, such as the use of furosemide, hemodialysis and digoxin-specific antibodies are reviewed. Supportive management may include treatment with atropine, phenytoin, lidocaine, propranolol, glucose, insulin and sodium polystyrene sulfonate. Proper management of digoxin poisoning involves the use of standard decontamination procedures (emesis or gastric lavage). Activated charcoal is strongly recommended, followed by rapidly acting cathartics. Antiarrhythmic therapy usually involves atropine sulfate and phenytoin sodium.

Acute Disease↗

Treatment of chronic portal systemic encephalopathy with bromocriptine: a double-blind controlled trial.

A randomized double-blind clinical comparison of bromocriptine, a new dopamine agonist, and placebo was performed on 7 cirrhotic patients with chronic portal systemic encephalopathy (PSE). Before given either medication, patients were stabilized with a standard treatment (neomycin and cathartics). Serial semiquantitative assessments were done, including mental state, asterixis, number connection test, electroencephalogram, and ammonia blood levels. Three patients developed signs of precoma while ingesting both placebo and bromocriptine. Two patients experienced precoma only with placebo, and another patient only while taking bromocriptine. One patient remained awake throughout the study. All patients responded initially to neomycin and cathartics. Bromocriptine proved not to be significantly superior to placebo and was always inferior to standard treatment. During treatment with bromocriptine, 3 patients experienced constipation. This may be partially responsible for the ineffectiveness in the treatment of PSE.

Ammonia↗

Comparative effects of lactulose and magnesium sulfate on urea metabolism and nitrogen excretion in cirrhotic subjects.

In previous studies with cirrhotic subjects administration of oral lactulose caused a reduction in the urea production rate associated with an increase in fecal nitrogen excretion. The change in urea production rate in response to lactulose therapy was an indirect measure of a reduction in total gut ammonia production. In this study, the effect of magnesium sulfate administration was compared with lactulose therapy in 5 cirrhotic subjects to determine whether the effects of lactulose on nitrogen metabolism might be attributed to a nonspecific, cathartic effect. Both magnesium sulfate (5-15 g/day) and lactulose (40-80 g/day) caused significant and comparable increases in stool weight, solids, and total nitrogen. Only lactulose caused a reduction in fecal pH. Magnesium sulfate had no significant effect on the urea production rate or urinary nitrogen excretion, whereas lactulose caused a 25% reduction in the urea production rate and an 18% reduction in urinary nitrogen excretion. The latter was accounted for by a fall in urinary urea. Nitrogen balance was more negative during magnesium sulfate than during control or lactulose periods since magnesium sulfate increased fecal nitrogen without altering urinary nitrogen excretion. These data demonstrated that the effects of lactulose on nitrogen excretion and urea metabolism were not duplicated by equivalent cathartic doses of magnesium sulfate.

Disaccharides↗

Botulism in Alaska, 1947 through 1974. Early detection of cases and investigation of outbreaks as a means of reducing mortality.

Since 1947, there have been 21 outbreaks of botulism in Alaska, involving 46 people with 13 deaths (28% fatality). In the last six months of 1974, there were four outbreaks. With one exception to date, type E toxin was involved in all outbreaks for which laboratory confirmation has been obtained, and in all instances, Eskimo and Indian foods were the source. Clinical signs and symptoms of nausea and vomiting, dysphagia, diplopia, dilated pupils, and dry throat occurred with great frequency, forming a diagnostic pentad. We recommend that treatment include close medical supervision, supportive care, and the use of antitoxin, cathartics, and possibly, penicillin. The source of an outbreak must be determined to prevent further cases. Only prompt recognition, therapy and epidemiologic investigation can reduce the death toll from botulism.

Adolescent↗

Cell-transforming activity and genotoxicity of phenolphthalein in cultured Syrian hamster embryo cells.

Phenolphthalein is a cathartic agent widely used in non-prescription laxatives. For the simultaneous assessment of in vitro carcinogenicity and mutagenicity of phenolphthalein, the ability of this chemical to induce cell transformation and genetic effects was examined using the Syrian hamster embryo (SHE) cell model. Cell growth was reduced by treatment with phenolphthalein at 10-40 microM in a dose-related manner. Treatment with phenolphthalein for 48 hr induced a dose-dependent increase in morphological transformation of SHE cells. Over the dose range that resulted in cell transformation ( 10-40 microM), treatment of SHE cells with phenolphthalein induced gene mutations at the hprt locus but not at the Na+/K+ ATPase locus. A statistically significant level of chromosomal aberrations was elicited in SHE cells treated with phenolphthalein at the highest dose (40 microM). Meanwhile, neither numerical chromosomal changes nor DNA adduct formation, analyzed by the nuclease P1 enhancement version of 32P-post-labeling, were induced by treatment with phenolphthalein at any concentrations examined. We thus report cell-transforming activity and mutagenicity of phenolphthalein assessed with the same mammalian cells in culture. Our results provide evidence that phenolphthalein has cell-transforming and genotoxic activity in cultured mammalian cells. The mutagenic and clastogenic activities of phenolphthalein could be a causal mechanism for carcinogenicity in rodents.

Animals↗

Saline catharsis: effect on aspirin bioavailability in combination with activated charcoal.

The effect of a saline cathartic combined with activated charcoal or activated charcoal alone on aspirin bioavailability was characterized in six healthy volunteers. Using a random, Latin-square design, subjects were given 975 mg aspirin followed by either water alone, 15 Gm activated charcoal (AC), or 15 Gm activated charcoal plus 20 Gm sodium sulfate (AC + SS) separated by one week. Both AC (44.16 +/- 16.85 microgram/ml) and AC + SS (58.61 +/- 10.63 microgram/ml) decreased (P less than 0.001) the maximal plasma salicylate concentration (Cpmax) compared to control (86.61 +/- 12.69 microgram/ml). Urinary salicylate recovery was decreased (P less than 0.01) for AC (57.88 +/- 16.26 per cent) and AC + SS (61.00 +/- 11.49 per cent) as compared to control (93.73 +/- 6.83 per cent), while for area under the plasma concentration-time curve (AUC) only AC showed a decrease (P less than 0.01) compared to control. Neither AC nor AC + SS differed from each other for Cpmax, AUC, or cumulative urinary recovery. Our findings indicate that the addition of sodium sulfate to activated charcoal has no added effect on limiting aspirin adsorption relative to activated charcoal alone.

Adult↗

Current preoperative bowel cleansing methods. Results of a survey.

A mail survey of 300 members of The American Society of Colon and Rectal Surgeons (ASCRS) was conducted to document the current methods of bowel preparation in use. Two hundred six questionnaires (69 percent) were returned. The majority of respondents (104 or 51 percent) used cathartics and enemas as the primary method of mechanical bowel cleansing. Eighty-nine (43 percent) used a PEG lavage, eight (4 percent) used mannitol, and one physician used a saline lavage method. Almost all the responding surgeons believed that their method of preparation was well tolerated by patients, provided good cleansing, and was associated with few complications. Most patients were admitted one day before surgery. All respondents used perioperative antibiotics, with the most common pattern being a combination of oral and parenteral agents. Surgeons using PEG lavage did more colonic resections per month and were fewer years out of their residency. This current pattern of preoperative bowel preparation has changed from previous surveys.

Anti-Bacterial Agents↗

Adverse effects of laxatives.

Laxatives are among the most commonly used drugs or additives. Most are quite safe when used judiciously, intermittently when possible, and in the absence of contraindications. Bulking agents and nonabsorbable compounds such as lactulose can cause bloating but have very few serious adverse effects except for the allergic reaction to psyllium preparations. Osmotic laxatives containing poorly absorbable ions such as magnesium or phosphate can cause metabolic disturbances, particularly in the presence of renal impairment. However, if taken intermittently, in the absence of conditions such as ileus or bowel obstruction, they have few adverse effects. Polyethylene glycol solutions are emerging as an effective and safe mode of treatment for chronic constipation. Of stimulant laxatives, senna compounds and bisacodyl are the most commonly used. Although there are data to support the neoplastic potential of this class of drugs in in vitro studies, epidemiologic data in humans so far has not established a clear link between these laxatives and colonic neoplasia. The link between stimulant laxatives and structural changes, such as the "cathartic colon" or enteric nerve damage, is not well established either. Danthron compounds should be avoided because of hepatotoxicity.

Cathartics↗

Melanosis of the rectum in patients with chronic constipation.

In patients with constipation the prevalence of melanosis in rectal biopsies was evaluated in an attempt to correlate its occurrence with laxative consumption and intestinal stasis. Melanosis was present in 58 percent of the patients and in none of a control group. Melanosis was present in 73.4 percent of patients consuming anthracene laxatives and in 26.6 percent of those not consuming anthracene laxatives (P less than 0.01). No correlation was found between the occurrence (and grading) of melanosis and pattern of transit through the large bowel, bowel movements, and duration of symptoms. Results of this study seem to indicate that intestinal stasis is not a cause of melanosis of the colon and rectum and confirm that melanosis may well be due only to the consumption of anthracene laxatives; melanosis coli does not appear to be a sensitive marker of impairment of motor function in the "cathartic colon."

Adolescent↗

A rapid high-performance thin-layer chromatographic urine screen for laxative abuse.

Laxative abuse, if unrecognized, can lead to unnecessary and costly investigations. The stimulants and cathartics are the most commonly abused laxatives and have the potential for causing the most long-term damage. We have optimized a solid-phase extraction coupled with high-performance thin-layer chromatography (HPTLC) to provide rapid, simple, and sensitive detection of phenolphthalein, danthron, rhein, aloin, and bisacodyl and its metabolites in urine. Positive screens have revealed laxative abuse in 3 of 42 samples from patients presenting with diarrhea of unknown origin.

Anthraquinones↗

Therapeutic efficacy of superactive charcoal in rats exposed to oral lethal doses of T-2 toxin.

Superactive charcoal, a compound known to complex with many toxins, was evaluated in this study for its effectiveness in preventing death in rats given an oral lethal dose of 8 mg/kg body weight of T-2 toxin. The median effective dose of oral superactive charcoal in preventing deaths in rats was 0.175 g/kg body weight. Concurrent use of cathartics, such as sorbitol, magnesium sulfate and sodium sulfate, to facilitate removal of the superactive charcoal:T-2 toxin complex formed in vivo did not enhance the survival rates of rats. One gram per kilogram body weight oral superactive charcoal enhanced survival times and survival rates in rats given 8 mg/kg of T-2 toxin as late as 3 hr after the T-2 toxin was administered. Some benefit in survival rate may be derived from giving the superactive charcoal as late as 5 hr after the T-2 toxin.

Administration, Oral↗

Gastric lavage.

Gastric lavage has been used to manage toxic ingestions since the early 1800s. The entire realm of gastrointestinal decontamination has been extensively studied for the past 30 years. Recommendations are still evolving and remain controversial. The current indications for lavage are obtundation, unprotected airway, seizures, the need for urgent removal, and the tendency to form concretions. Hydrocarbon management depends on specific toxicity and viscosity. Contraindications for this procedure are insignificant ingestions, prolonged time since ingestion, and caustic poisoning. Proper technique minimizes complications and maximizes toxin removal. Activated charcoal and a cathartic are given after lavage. Complications include nasal trauma, esophageal perforation, tracheal intubation, aspiration, electrolyte imbalance, and hypothermia.

Cathartics↗

Potassium supplements prevent serious hypokalaemia in colon cleansing.

The association between colonic cleansing and hypokalaemia was studied prospectively by monitoring the serum potassium levels in four groups of patients: groups 1 (55 patients), 2 (72 patients), and 3 (97 patients) received the same 2-day preparation of 15 g magnesium sulphate and 10 mg bisacodyl twice daily; group 4 (96 patients) received a 1-day preparation of 2.4 mg sennoside per kg of bodyweight. Groups 1 and 2 were on diuretics, but only group 2 received potassium supplementation. Serum potassium levels were measured before and after bowel preparation. Hypokalaemia was present prior to cleansing in six (11%), and after cleansing in 20 (36%) of the 55 patients in the group 1 patients on diuretics but without potassium supplements. There was, after cleansing, no significant fall in serum potassium in the group 2 patients on diuretics who received potassium supplements. No hyperkalaemia resulted from supplementation. A significant fall of the mean level of serum potassium occurred in patients in both group 3 (2-day-preparation) and group 4 (1-day-preparation). We conclude that both 1 day and 2 days of cleansing with cathartics may result in a significant fall in serum potassium, which can be prevented by oral potassium supplements. Potassium supplements (three times a day 15 ml of potassium chloride with 0.9 mmol K per ml during the preparation) in patients on diuretics may be prudent to avoid the risk of cardiac arrhythmia.

Aged↗

Advances in clinical toxicology.

New data are reviewed in two areas in the management of the acute overdose: gastrointestinal decontamination and systemic antidotes. The mechanism and effectiveness of Ipecac syrup, gastric aspiration and lavage, activated charcoal, gastrointestinal dialysis, and saline cathartics are discussed. Special problems posed by disc batteries and packet ingestion of cocaine (in transporting contraband) are highlighted. The pharmacology and uses of pyridoxine and naloxone as antidotes are detailed.

Antidotes↗

Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution.

Evidence is emerging that sodium phosphate (NaP), a commonly used oral cathartic agent, causes aphthoid ulcers or focal active colitis (FAC) in the colon and rectum. The aims of this study were (1) to assess the incidence of such ulcers diagnosed endoscopically ("aphthoid ulcers"), (2) to assess the incidence of histologically detected FAC and neutrophilic infiltration overlying lymphoid follicles ("aphthoid lesions"), and (3) to determine whether this effect of NaP is associated with epithelial cell proliferation. Aphthoid ulcers, unexplained by other diagnoses, were found in 18 of 687 consecutive patients (2.6%) who underwent colonoscopic examination after oral NaP preparation during a 12-month period; biopsy specimens showed FAC or aphthoid lesions. FAC was present in 11 of 316 patients (3.5%) who had biopsies but were endoscopically normal. Eight patients with aphthoid ulcers in the rectosigmoid showed no abnormalities when reexamined by flexible sigmoidoscopy after an interval as short as 7 days (range, 7 to 56 days). Mucosal biopsy specimens from these patients were assessed for apoptosis and epithelial proliferation by determining the MIB-1 labeling index (LI). The LI was increased by 136% after NaP preparation (55 +/- 6) compared with biopsy specimens obtained from the same patients during reexamination without NaP preparation (23 +/- 6, P = .01). This correlated with the number of apoptotic bodies per 10 colonic crypts (1.2 +/- 0.3 v 0.5 +/- 0.2, respectively). To determine whether these proliferative changes represent a response to mucosal ulceration, rectosigmoid biopsy specimens were compared in two additional patient groups: an NaP group in whom no gross lesions were evident and a no-NaP group who were not exposed to NaP. Although more modest, similar changes in the LI (42 +/- 4 and 30 +/- 3, respectively, P = .03) and in the occurrence of apoptotic bodies per 10 colonic crypts (1.3 +/- 0.4 and 0.4 +/- 0.1, respectively) were observed. We conclude that use of NaP is associated with increased colorectal crypt epithelial cell proliferation. This proliferative response to NaP exposure is evident in the absence of colonoscopically or other histologically recognizable abnormalities. In a proportion of patients, aphthoid ulcers, FAC, or aphthoid lesions serve as markers of mucosal damage by NaP.

Administration, Oral↗

Acute hypermagnesemia after laxative use.

We present the case of a patient in whom hypotension, sudden cardiopulmonary arrest, and coma developed after a massive dose of a seemingly harmless cathartic agent. The diagnosis of hypermagnesemia was made 9 hours after the patient's admission, when the serum magnesium concentration was 21.7 mg/dL (8.9 mmol/L). The patient's condition improved with IV calcium, saline solution infusion, and cardiorespiratory support. The elimination half-life of magnesium in this case was 27.7 hours. Few cases have been reported in which patients have survived with serum levels greater than 18 mg/dL (7.4 mmol/L). This case provides evidence that hypermagnesemia may occur in patients with normal kidney function. The diagnosis of hypermagnesemia should be considered in patients who present with symptoms of hyporeflexia, lethargy, refractory hypotension, shock, prolonged QT interval, respiratory depression, or cardiac arrest.

Acid-Base Imbalance↗