Also posted over at Paramedicine 101 and at Research Blogging.
Go check out the rest of the excellent material at both sites.
Continuing from yesterday’s discussion of the problems with highly concentrated dextrose – Should EMS Still Use 50% Dextrose we will look at some research –
Dextrose 50% is a hypertonic solution of glucose available in prefilled syringes containing 25 g glucose in 50 ml water (IMS mini-jet, International Medication Systems (UK), Leatherhead, Surrey, England). In south-east Wales, at the time of this study, it was administered intravenously in 5–10 g (10–20 ml) increments, titrated against effect after confirming hypoglycaemia by capillary or venous blood sugar level.
This is a bit different from the American protocols I am used to, which generally have only specified a dose of 25 gm followed by reassessment of blood sugar and a possible second dose or a different treatment. This does appear to be similar to the way that I have treated unconscious hypoglymic patients – pulling back on the plunger to assess for blood return (an indication that the IV catheter is properly placed within the vein) and slowly pushing, but they are giving twice as much as I would at any single time.
An important point is that the participating EMS agencies realize that supplementing the patient’s dietary dextrose with intravenous dextrose means we are giving a drug and that drug should be titrated to effect. The same is true of supplemental oxygen. We need to recognize that these are drugs that have significant side effects. For too long, we have ignored these side effects and have been irresponsibly presuming that these treatments are harmless, in spite of risks that appear to include permanent disability and death.
This randomised controlled trial aimed to compare the efficacy and safety of 5 g aliquots of 10% and 50% dextrose in the out of hospital treatment of adult hypoglycaemic patients.
5 gm of 10% dextrose = 50 ml.
5 gm of 50% dextrose = 10 ml.
To ensure that the dose of 10% dextrose was measured accurately, the paramedics used a syringe attached to a three-way tap to draw up 50 ml aliquots from a 500 ml infusion bag attached to a giving set. The 10 ml aliquots administered to the 50% dextrose group were measured using 5 ml calibration markings on the prefilled syringes. The paramedics were instructed to administer the 5 g bolus and wait for one minute before administering subsequent aliquots, until either the Glasgow Coma Scale (GCS) score had returned to 15 or the maximum cumulative dose of 25 g of dextrose had been administered. Time taken to regain GCS 15 was calculated from the time the first incremental dose was administered.
Due to the confused or unconscious state of hypoglycaemic patients it was not possible to obtain informed consent from the participants prior to recruitment into the trial. Instead, when they were recovered and oriented after treatment, the paramedics informed them that they had been recruited for a study that was comparing the efficacy of two different concentrations of dextrose. Each participant was given an information pack describing the trial with a form and preaddressed envelope so that participants could withdraw their data from the study at any time. Ethical approval was obtained from the Bro Taf Health Authority Local Research Ethics Committee.
Amazing. None of the whining about withholding the Standard of Care that discourages evaluation of treatments that have become Standard of Care because they are traditional treatments, rather than safer and more efficacious treatments than other treatments.
Following a pilot study, it was established that a total sample size of 50 was required (25 subjects per group) to detect a three minute difference between the groups in a return to full consciousness (GCS 15), with power of 0.85 and α of 0.05.
That is the big deficiency of this study. The sample size is too small, unless the only reason for studying this is to determine if the difference in time of the treatments is statistically significant.
Is this due to a mistaken concern that the availability of the paramedic to the next patient, and the possible delay in response time, is more important than the complications of treatment? Then there are many treatments that we should abandon for taking too much time. Why treat these patients at all, when we can just throw them in the ambulance and beat feet to the hospital?
On the other hand, if we accept that the treatments provided by paramedics are expected to be both efficacious and safe, then the size of this sample does not evaluate that question.
To turn the question around, is the current treatment of hypoglycemia with 50% dextrose safe enough?
By switching to a less concentrated dextrose solution, do we significantly improve safety?
This is a much more important question than whether switching to 10% dextrose for hypoglycemia will slightly delay the patient’s return to consciousness or slightly delay the paramedic’s return to availability. If there were some evidence that paramedic response times made a difference in outcomes, small differences in treatment time might be important.
While the difference in treatment time is subtle, the difference in concentration of the solutions is not remotely subtle. This is where the focus of the study should be.
Would a 1% rate of tissue necrosis be important?
If the rate of tissue necrosis from infiltration is 1% with 50% dextrose, is this study designed to evaluate that?
Would a 1% rate of rebound hypoglycemia be important?
If the rate of rebound hypoglycemia is 1% with 50% dextrose, is this study designed to evaluate that?
Is there a significant difference in complications between 10% dextrose and 50% dextrose?
If there were a significant difference in the complications, wouldn’t it justify a significant difference in treatment time?
It may seem reasonable to conclude that I am not happy with the research. That is not true. My criticism of the research that has been done is insignificant compared to my criticism of the lack of research by others.
Our criticism should be addressed to the medical directors who give hundreds of doses a year of 50% dextrose through their paramedics with no assessment of outcomes and no consideration of research to demonstrate efficacy and safety. Further criticism should be addressed to the FDA (Food and Drug Administration) for discouraging emergency research. Other criticism should be directed at the administrators and lawyers who discourage us from even asking if we are harming our patients with the Standard of Care.
C. Moore and M. Woollard deserve our thanks and praise for raising the question of why we are giving such highly concentrated dextrose without evaluating the comparable safety and efficacy of much less concentrated dextrose solutions.
After all of that ranting, what are the results of the study?
Time on scene was moderately higher for the 10% dextrose group, and paramedics rated administration of 10% dextrose as being slightly less easy than for the 50% solution. However, neither finding reached statistical significance. There were no reported incidences of extravasation in either group.
The difficulty is due to the method of administration used in this study. There are many other methods that might be used. We can expect that some innovative paramedics will come up with acceptable ways of giving 10% dextrose that are not slightly less easy than giving 50% dextrose.
Both the median total dose of dextrose administered and post-treatment blood sugar level were significantly higher in the 50% group, and these subjects were more likely to have received the maximum permitted dose of 25 g (table 2).
Imagine if we found out that using a different concentration of morphine produced a statistically significant difference in the total dose of morphine given. Morphine is a very safe drug that is only perceived as unsafe by inexperienced medical directors and by other inexperienced people.
Or substitute fentanyl, or diazepam, or lorazepam, or midazolam, . . . . for morphine in that sentence.
Fentanyl, diazepam, lorazepam, midazolam, . . . are very safe drugs that are only perceived as unsafe by inexperienced medical directors and by other inexperienced people.
An exploratory analysis of patients without a maximum GCS score of 15 following treatment is shown in table 3. Although all three patients had euglycaemic post-treatment blood sugar levels, all required hospital admission. One of these patients was suspected of being under the influence of illegal drugs, one was a known alcoholic, and one had a serious intercurrent urinary tract infection.
Look at the blood sugar levels.
11.4 mmol/l is 205 mg/dl. Would this patient continue to be treated with dextrose, if the patient had been receiving 50% dextrose?
9.7 mmol/l is 175 mg/dl. Would this patient continue to be treated with dextrose, if the patient had been receiving 50% dextrose?
8.7 mmol/l is 157 mg/dl. Would this patient continue to be treated with dextrose, if the patient had been receiving 10% dextrose?
The patients did not become alert, even though their blood sugar levels increased well beyond the normal range. These do not appear to have anything to do with either concentration of dextrose.
Two of the subjects contacted by the researchers after treatment reported that before the study they had often had difficulty bringing their blood glucose back to their expected usual level after being treated by paramedics using 50% dextrose. This might imply that the lower cumulative doses administered with the 5 g (50 ml) aliquots of 10% dextrose could assist patients in controlling their post-treatment blood sugar levels. Evidence suggests that administration of dextrose can have a detrimental effect on patients at risk of cerebral ischaemia, such as victims of stroke, cardiac arrest, or head trauma.7 Avoidance of hyperglycaemia has a neuroprotective effect and reduces mortality and morbidity in the critically ill.14 15 The relatively lower post-treatment blood sugar levels associated with the use of 10% dextrose administered in 5 g (50 ml) aliquots may, therefore, offer a safer option for the treatment of hypoglycaemia in these categories of patient.
Are we harming our patients by giving such high doses of highly concentrated dextrose?
Does 50% dextrose predispose patients to adverse effects?
If we base our answers on what we know about pathophysiology (examples given in the above quote), we should conclude that the continuing use of 50% dextrose is not justifiable.
We use our knowledge of pathophysiology to justify treating cardiac arrest patients with epinephrine, amiodarone, and lidocaine.
Why do we use our knowledge of pathophysiology to support giving treatments that are not based on evidence to patients who will probably not survive their cardiac arrest, when we do not use the same knowledge to limit ourselves to safer and readily available treatment for hypoglycemia who are expected to survive their hypoglycemia?
 Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial.
Moore C, Woollard M.
Emerg Med J. 2005 Jul;22(7):512-5.
PMID: 15983093 [PubMed - indexed for MEDLINE]
To convert mmol/l of glucose to mg/dl, multiply by 18.
To convert mg/dl of glucose to mmol/l, divide by 18 or multiply by 0.055.
Moore, C. (2005). Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial Emergency Medicine Journal, 22 (7), 512-515 DOI: 10.1136/emj.2004.020693