In the Literature

The Hospitalist. 2006 July;2006(07):

July 1, 2006 | The Hospitalist

Jeff Glasheen, MD, FHM ; Ethan Cumbler, MD ; Jeffrey Carter, MD ; Jeanie Youngwerth, MD ; Whitney Woodmansee, MD ; William Rifkin, MD

An ICU patient database was analyzed for cost data related to intensive glycemic control. A baseline group of 800 consecutive ICU patients admitted prior to initiation (baseline) of an intensive glucose management (blood glucose levels between 80-140 mg/dl protocol were compared with a treatment group of 800 consecutive patients admitted after initiation of the protocol). Previously reported outcomes of these patients demonstrated significant improvement in mortality with tight glycemic control. Costs related to ICU and non-ICU length of stay; duration of mechanical ventilation; and all laboratory, pharmacy, and radiology services were analyzed between groups. Resource utilization was determined by assessing charges from the database and adjusting for inflation and applying Medicare cost, charge ratios for each category, and fiscal year. Costs associated with the intensive glycemic control protocol were determined. Unfortunately, only cost estimates for insulin and associated disposable supplies for each group were available for analysis.

Baseline and treatment populations did not differ significantly regarding demographics such as age, gender, race, admitting diagnosis, diabetes prevalence, or APACHE II scores. There were fewer patients in the treatment group that required mechanical ventilation during their ICU stay (40.6% versus 33.6%). Intensive glucose management was associated with a 13.9% reduction in total ICU days and duration of mechanical ventilation (median of two days decreased to 1.7 days p=0.045). There was a $1,580 adjusted cost savings per patient in the intensive treatment group compared with the baseline group (p<0.001). This reduction in cost was primarily driven by a decrease in laboratory and radiology costs in the ventilated patients. There were nonsignificant cost reductions in the unventilated patients.

Intensive control of hyperglycemia in the hospitalized ICU patient appears to be associated with reduction of morbidity and mortality. This suggests that tight glycemic control also leads to reductions in overall patient care costs—particularly in the ventilated ICU patient. Although not a randomized control trial, database analysis of costs and resource utilization demonstrated an overall cost savings in the treatment group (after initiation of an intensive glycemic control protocol) compared with the baseline group (before protocol initiation). One caveat is that the authors used estimates when determining the costs associated with the implementation of the intensive glucose management protocol. Nevertheless, intensive glycemic control was associated with an overall reduction in patient costs related to decreased ICU days and mechanical ventilation as well as resource utilization in a patient population already shown to have improved mortality. These results, if confirmed, suggest that tight glycemic control in the ICU is cost effective and should become standard medical practice. TH

Classic Literature

Beat the Heroin Habit

By William Rifkin, MD

Dole VP, Nyswander M. A medical treatment of diacetylmorphine (heroin) addiction. JAMA. 1965 Aug 23;193:80-84.

This article is the 12th most cited article from JAMA in the 1960s. It had been cited 473 times as of April 2006, an average of almost once a month since publication. Forty-seven citations have occurred since 2000, most recently in January 2006.

Background/Methods

The authors examined “whether a narcotic medicine, prescribed as part of a treatment program, could help in the return of addict patients to normal society.” This was the first study on such a practice.

The patients were simply described as “22 non-psychotic heroin users … with a history of failures of withdrawal treatment.” They were further classified as Western European, Puerto Rican/Cuban, or black.

Examined range of time in methadone treatment was one week to 15 months.

Results

Presented in narrative format; “The most dramatic effect … has been the disappearance of narcotic hunger.” Further, “ … patients found that they could meet addict friends and even watch them inject without great difficulty. … They have stopped dreaming about drugs … have even become so indifferent to narcotics as to forget to take a scheduled dose … .”

The degree of tolerance was tested in six patients, “ … by giving heroin, morphine, Dilaudid or methadone intravenously in a double blind study.”

They described the use of non-prescribed narcotics as “ … unscheduled, but perhaps necessary, experiments in drug usage made by four patients. These subjects found that they did not ‘get high’ … patients and their friends were astounded at their lack of reaction … .”

As an aside the authors note that constipation was assessed by giving five patients a barium sulfate meal and following daily X-ray exams for a week.

Conclusion/Commentary

“Maintenance with methadone is no more difficult than maintaining diabetics with oral hypoglycemic agents … .”

One should note that this was an uncontrolled case series. As such it is very low in the hierarchy of study strength to make firm conclusions. Yet the authors do, most emphatically by today’s standards.

I am astounded by the difference of acceptable research behaviors and standards 40 years ago with those of today. Firstly, what were the ethics of giving patients IV heroin, especially with no mention of informed consent or an IRB. Secondly, note the cavalier attitudes to radiation evidenced by a side examination of constipation via a barium meal and daily X-rays.

Finally, I am quite surprised that a study with the below outlined threats to validity, which, although it could be argued render the data meaningless, is one of the most cited and referenced articles in the whole medical literature, let alone in the specific area of narcotic replacement therapy.

By today’s standards for scientific rigor, one should note that no data were presented. This was simply a descriptive narrative of experiences as reported by the physician authors of their patients. Further the median duration in the program was only three months. Ten of the 22 patients were treated for less than six weeks—two for less than 14 days. Nevertheless, the authors make dramatic conclusions about a chronic disease.

Obviously we should be careful about applying 21st century standards of science and ethics to a 40-year-old study. However, it does give pause that at least as recently as 1965 it appears researchers were granted relatively free rein by society to perform studies on patients and by editors of a medical publication to make dramatic conclusions.

In the case of methadone, of course, time has tempered the exuberant optimism on display here. Narcotic replacement therapy is clearly useful, but, alas, patients hardly “… forget about scheduled doses …” and treatment would not be classified as “… no more difficult than maintaining diabetics with oral hypoglycemic agents … .” TH