DEPT OF ERROR

The patient whose hypocalcaemia worsened after prompt
intravenous calcium replacement therapy
Piero Stratta, Giorgio Soragna, Veronica Morellini, Massimo Gai, Daria Motta,Elisa Lazzarich, Maddalena Brustia, Marco Quaglia,Caterina Canavese
LANCET JAN. 21, 2006
As a junior in the emergency department, I saw a 30-year-old man with severe numbness, tingling in the fingers and toes and perioral area, muscle cramps, and tetany; he had chronic hypoparathyroidism, due to thyroidectomy, which was being treated with oral replacement of thyroid hormones, calcium, and vitamin D. He had been unable to take his regular treatment over the past few weeks because of gastroenteritis.

Blood tests showed a low total calcium of 1·125 mmol/L ( ie equal to 4.4 mg/dl in American terms: kk) (free ionised portion 0·51 mmol/L), phosphate 1·8 mmol/L,creatinine 88·4 mol/L, urea 3·57 mmol/L, sodium139 mmol/L, potassium 4·5 mmol/L, blood bicarbonate29 mmol/L, and pH 7·4.

Because of the severe hypocalcaemia, I chose intravenous calcium replacement according to the formula: 1–2 mg/kg per h (body-weight 50 kg) of calcium. Using ampoules of 10 mL10% calcium gluconate, I assumed that each ampoule contained 1 g (1000 mg) of calcium. I diluted the 10 mL ampoule into 500 mL 5% dextrose, calculating that each mL of this solution contained almost 2 mg of calcium(1000 mg in 510 mL=1·96 mg/mL). The infusion was scheduled at 50 mL/h for the next 10 h, delivering 98 mgof calcium per h (1·96 mg/mL at 50 mL/h); this schedule met the requirement of 1–2 mg/kg per h, as the patient weighed 50 kg.

3 h later, my consultant took me to the patient’s bedside; the young man had complained of carpopedal spasm, laryngeal spasm, and bronchospasm, and 1 h earlier he had had other typical signs of hypocal-caemia—namely, a focal seizure, arrhythmia, and prolongation of the Q-T interval. His ionised calcium concentration had decreased further to 0·49 mmol/L.

Unfortunately, my calculation of calcium replacement had been incorrect: the replacement assumed that calcium gluconate was constituted only by elemental calcium; in the formula the replacement therapy is expressed as mg of elemental calcium and not mg of calcium salt. Calcium gluconate is the calcium salt of gluconic acid, and contains only 9 mg/mL elemental calcium (table). Therefore, each ampoule of 10%calcium gluconate contained 1000 mg of calcium gluconate, but only 90 mg of elemental calcium.

100–360 mg of elemental calcium should be given over5–10 min in cases of life-threatening hypocalcaemia(free ionised calcium 0·59 mmol/L), followed by a1–2 mg/kg per h of elemental calcium. This means that one to four 10 mL ampoules of 10% calcium gluconate should have been used in our patient, as this dose raises the concentration of ionised calcium by 0·5 mmol/L. We applied this dosing-schedule to our patient, followed by an infusion of 50 mL (five ampoules) of 10% calcium gluconate diluted in 500 mL 5% dextrose (450 mg elemental calcium); the 550 mL solution contained0·8 mg of elemental calcium per mL of solution.Therefore, an infusion of 100 mL/h provided 80 mg/h of elemental calcium—equivalent to 1·6 mg/h of elemental calcium for each kg of bodyweight. IE: five ampoules in 500 ml to run 100 cc an hour that is how you treat life threatening hypocalcemia- kk- The patient’s condition gradually improved over 24 h.

Of note, calcium chloride salt is second line choice for treatment of hypocalcaemia, unless there is severe alka-losis, as it causes more tissue necrosis if extravasated.

My mistake will haunt me for the rest of my professional life. When replacing electrolytes, it is important to bear in mind the absolute need to understand basic chemistry, calculate replacement in Standard International Units, replace element and not salts, and to refer to the hospital formulary when in doubt. Lancet 2006; 367: 273

Nephrology andTransplantation, Departmentof Nephro-Urology, AmedeoAvogadro University, OspedaleMaggiore della Carità, CorsoMazzini 18, 28100 Novara,Italy (Prof P Stratta,V Morellini MD,E Lazzarich MD,M Brustia MD, M Quaglia MD,C Canavese MD); andDepartment of InternalMedicine, Section ofNephrology, University ofTorino, Molinette Hospital,Corso Bramante 88, 10126Torino (G Soragna MD, M Gai MD,D Motta MD)Correspondence to:Prof P Stratta strattanefro@hotmail.comThe patient whose hypocalcaemia worsened after promptintravenous calcium replacement therapyPiero Stratta, Giorgio Soragna, Veronica Morellini, Massimo Gai, Daria Motta,Elisa Lazzarich, Maddalena Brustia, Marco Quaglia,Caterina Canavese

Calcium salt Formula Molecular Elemental calcium Elemental Calcium weight(Ca2) mg(Ca2) mmol

Calcium gluconate C12H22CaO14430·3890 mg per2·3 mmol per10% injection 10 mL10 mL10 mL ampouleampouleampoule(1000 mg per 10 mL)/ but only 90 mg per ampoule
Calcium chlorideCaCl2110·98270 mg per6·8 mmol per10% anhydrous injection 10 mL 10 mL10 mL ampoule(1000 mg per 10 mL) but
rino, Molinette Hospital,Corso Bramante 88, 10126Torino (G Soragna MD, M Gai MD,D Motta MD)Correspondence to:Prof P Stratta strattanefro@hotmail.com
7:11 AM

DID YOU KNOW TRAZODONE IS GOOD SLEEPER AGENT?

FROM NEW YORK TIMES May 9, 2006



Generic Smear CampaignBy DANIEL CARLAT
Published: May 9, 2006
Newburyport, Mass.

THAT pharmaceutical companies pay doctors to say good things about their drugs is no longer newsworthy. Two former editors of The New England Journal of Medicine, Jerome P. Kassirer and Marcia Angell, have documented the drug industry's use of doctors to promote new medicines through professional articles and at medical conferences.

But in a move that may astonish even the most jaded critics of ethically challenged pharmaceutical marketing, makers of sleeping pills are now paying doctors to publish bad things about competing drugs.

The market for sleeping pills is huge — 42 million prescriptions were filled last year — and it is more competitive than ever, thanks to the recent introduction of Sepracor's Lunesta (the one with the butterfly commercials), Sanofi-Aventis's Ambien CR (a controlled-release version of Ambien) and Takeda Pharmaceuticals' Rozerem. Ads have made most of these drugs household names. Yet many people have never heard of one of the most widely prescribed hypnotics in the United States: trazodone.

First approved by the Food and Drug Administration 25 years ago, trazodone is categorized as an antidepressant. Nonetheless, psychiatrists prescribe it off label to treat insomnia, because it works so well. Trazodone carries no risk of addiction; its half-life is long enough to keep patients asleep all night; it has a long safety record; and it is cheap, costing as little as 10 cents a pill. (Ambien and Lunesta can cost $3 a pill or more.) And in the only sizable study to compare trazodone with Ambien as a sleep aid, the two drugs performed equally well.

But each time a psychiatrist prescribes trazodone, a potential sale of Lunesta or Ambien is lost. No doubt that is why, in the past few years, several articles have been published in professional journals that can only be described as trazodone-bashing. With titles like "The Use of Trazodone as a Hypnotic: A Critical Review" (published in The Journal of Clinical Psychiatry), these articles purport to present balanced reviews of the scientific literature on sleeping pills. But the authors, psychiatrists with university affiliations, have been paid by Sepracor, Sanofi-Aventis or Takeda, the companies that stand to gain from trazodone's downfall.

A disclosure statement at the top of one such paper, "A Review of the Evidence for the Efficacy and Safety of Trazodone in Insomnia," also in The Journal of Clinical Psychiatry, states that Sepracor "assisted in the preparation" of the article, and paid the author a fee for "the services he provided in support of the development" of the manuscript.

A careful reading of these articles reveals a pattern of rhetorical techniques: a minimization of trazodone's advantages and an emphasis on its negative qualities.

Trazodone is criticized as lacking high-quality research data on its ability to help people sleep. What is left unmentioned is that because trazodone is no longer patented, no pharmaceutical company stands to profit from doing such research .The authors also dust off older studies highlighting side effects from trazodone, like cardiac arrhythmias or priapism (prolonged painful erections). But these side effects are extremely rare: priapism has been found to occur in one in 5,000 men who take the drug, and the incidence of cardiac arrythmias is even lower.

Case reports of such side effects inevitably surface when a drug has been on the market for 25 years. In the case of Ambien, the oldest of the newer drugs, we are already seeing a flurry of reports of problems like drug abuse, sleepwalking, night eating and car accidents that may be associated with its use.

The way to discourage this practice of negative marketing disguised as legitimate scientific commentary is to mandate fuller disclosure of links between drug companies and authors. Several states now insist that drug makers report the gifts they give doctors.

These same companies should be required to disclose the exact nature of a doctor's involvement in preparing a sponsored article, as well as the dollar amount of his or her fee. I suspect it would be the rare doctor who would want such information to come to light.

Daniel Carlat, a professor at Tufts Medical School, is the editor in chief of The Carlat Psychiatry Report.


My comment : You bet most of us did not learn this from Medical School. Let us continue to learn together now. KK

WELCOME TO THE FORUM
This is a place for any MDs/DOs/ from north of the Tobin bridge to make any comments . It could be about any thing under the sun. The MDs do not have to be associated with any of the hospitals in the area.

Comments may be of any nature about any thing. You can make anonymous comments on this blog.

The hope is whatever opinions you give will be for the good of our physician group or north shore of Boston or MA, or world at large. Be good please. Our time in this world is limited, make use of it.

KK