Pyruvate dehydrogenase enzyme dipstick test in traumatic brain injury : A concern

I agree with the reader that complete evaluation of the dipstick test in the diagnosis of traumatic brain injury has to be done, and studies using various animal models with compromised mitochondrial functions are in progress in our laboratory. As stated in the original publication,[2] this dipstick test is highly sensitive when compared to the spectrophotometric test because only 25 μg protein is needed; the spectrophotometric method requires at least 50–75 μg protein, which can be a problem when only a small quantity of sample is available. Like any other diagnostic test, the dipstick test results may also vary with the type of tissue analyzed, method of tissue collection, handling and storage processes, as well as the underlying pathophysiological conditions. We are also examining the influence of these factors on pyruvate dehydrogenase activity in our current studies. Also, to avoid the pre-analytical error, we have standardized the cell lysis protocol and equal volumes of samples are being used to avoid variation in dipping techniques.

Sir, I am writing in response to the questions raised by one of our readers. [1]First, I would like to thank him for taking an interest in our publication. [2]Since the acceptance of this paper, we have generated some interesting data on how our dipstick test compares with conventional spectrophotometric tests for pyruvate dehydrogenase content and enzyme activity assessment.
I agree with the reader that complete evaluation of the dipstick test in the diagnosis of traumatic brain injury has to be done, and studies using various animal models with compromised mitochondrial functions are in progress in our laboratory.As stated in the original publication, [2] this dipstick test is highly sensitive when compared to the spectrophotometric test because only 25 µg protein is needed; the spectrophotometric method requires at least 50-75 µg protein, which can be a problem when only a small quantity of sample is available.Like any other diagnostic test, the dipstick test results may also vary with the type of tissue analyzed, method of tissue collection, handling and storage processes, as well as the underlying pathophysiological conditions.We are also examining the influence of these factors on pyruvate dehydrogenase activity in our current studies.Also, to avoid the pre-analytical error, we have standardized the cell lysis protocol and equal volumes of samples are being used to avoid variation in dipping techniques.
As indicated in the original article, the dipstick cost only $10 per test, can be done quickly, and is easy to do.In comparison, the conventional spectrophotometric test costs at least $50 per test and needs a trained scientist or technician to perform the pyruvate dehydrogenase measurement.
In conclusion, this dipstick test is in its early stages of development and we are working to validate the diagnostic capability of this potentially useful tool.and mentions that this alternative has many advantages over the classical spectrophotometric method. [1]Pathophysiologically, traumatic brain injury can induce expression and phosphorylation of pyruvate dehydrogenase, the specific rate-limiting enzyme coupling cytosolic glycolysis to the mitochondrial citric acid cycle. [2]Since the main function of pyruvate dehydrogenase is the maintenance of homeostasis of brain glucose metabolism, dysregulated glucose metabolism may be seen in traumatic brain injury. [2]Measurement of pyruvate dehydrogenase can be a useful laboratory investigation in the management of patients with traumatic brain injury.In laboratory medicine, the standard method for measurement of pyruvate dehydrogenase is based on the principle of enzymatic measurement [3] and the spectrophotometric method is generally used. [3]However, to perform a spectrophotometric measurement of the enzyme, a standard medical laboratory has to be available.Since traumatic brain injury is considered an emergency condition, an alternative method that can be used as a bedside or point-of-care test is required.In the paper by Sharma et al., [1] a new dipstick test was used and showed good results.However, there is a need to consider for the ability in laboratory diagnosis which include sensitivity, specificity, accuracy, predictive value and etc.Indeed, a complete evaluation of this new test has to be done.The diagnostic sensitivity and range of analysis (upper and lower limit for diagnosis) have to be tested.It is possible that the dipstick test might produce results that deviate from that obtained with the gold standard.This should be verified.In addition, based on the nature of dipstick, the pre-analytical error due to variation in the dipping technique is an important practical point that needs consideration.Due to the described reasone, a careful practice is needed for applying the test, dipping the test strip, into the specimen.The clinical diagnostic capability (sensitivity, specificity, and positive and negative predictive values) of this test in actual clinical practice is still to be established.In addition, the question of the cost-effectiveness of this alternative method as compared to the classical method has to be considered.This data is needed although Sharma et al. have given the direct cost of each test in their paper.These data will be useful for further decision making regarding the use of the new dipstick test.
Various modifications have evolved over the manipulation of cricoid with different intent, over the past few years.
'BURP' maneuver (consisting of backward, upward, and right-sided pressure on the thyroid and cricoid cartilages) was introduced by Knill in 1993 [13] to improve the glottic view during endotracheal intubation.Takahata et al. in their study proved the efficacy of BURP by demonstrating significant improvement of the glottic view during the attempts at endotracheal intubation in 630 cases. [15] 'Modified BURP' maneuver', the patient lies supine with a sniffing position.The thumb and middle finger are applied to the cricoid cartilage and the index finger is applied to the left hand side of the thyroid cartilage.Pressure is applied to both of these structures, downwards, superiorly, and to the right hand side.This maneuver was intended to be a combination of both Sellick's and the burp maneuvers. [13]Snider et al. were of the opinion that 'modified BURP' maneuver not only failed to enhance the glottic view during RSI but actually worsened it in 30% of cases, and that was because of improper application of cricoid pressure. [13]wever, understanding the basic purpose of two different maneuvers, the cricoid pressure and the laryngeal manipulation, Benumof coined a new term-OELM (optimal external laryngeal manipulation).He suggested that during laryngoscopy, the operator should manipulate the larynx (hyoid and thyroid cartilages only) with the free hand in an effort to improve the laryngoscopic view [Figure 2].In a study of 181 patients acting as their own controls, he demonstrated a significant improvement in the laryngoscopic view when OELM was applied. [13]nce, confusion, both among practicing anesthesiologists as well as trainee student medics of anesthesia and pediatric medicine, has to arise when one mentions that the most effective maneuver is the application of external pressure at the level of cricoid cartilage to push the larynx into view, [14] whereas another reference quotes that vigorous cricoid pressure can distort the laryngeal anatomy or inadvertently flex the neck, impairing intubation. [6]Further, some say that cricoid pressure prevents regurgitation; others mention that it improves laryngoscopic view.
The concept of the use of 'cricoid pressure' was originally intended to prevent aspiration particularly in the setting of emergency intubation.But now, pressure or manipulation of cricoid for whatever and however confusing its purpose may be is being designated the same term of 'cricoid pressure'.This is

Cricoid pressure -A misnomer in pediatric anaesthesia
Sir, Cricoid pressure, sometimes called Sellick's maneuver (or even 'The Sellicks'), is the application of backward pressure on the cricoid cartilage to occlude the esophagus [Figure 1].This maneuver prevents aspiration of gastric contents during induction of anesthesia and in resuscitation of emergency victims when intubation is delayed or not possible.
Although the application of cricoid pressure was originally described by Dr. Munro in 1774, it was not until 1961 when Dr. Brian Arthur Sellick, an eminent anesthetist, published his original paper "Cricoid pressure to control regurgitation of stomach contents during induction of anesthesia-preliminary communication" that the maneuver gained widespread acceptance.The recommended pressure to prevent gastric reflux is between 30 and 40 N (equivalent to 3-4 kg).However, pressures higher than 20 N cause pain and retching in awake patients and a pressure of 40 N can distort the larynx and complicate intubation.
Contrary to Arthur Sellick's concept, various authors were of the opinion that cricoid pressure in pediatric population, particularly neonates, improved glottic view and aided tracheal intubation apart from its classical role in rapid sequence intubation for