Morning MEDtalks with Dr KK Aggarwal 26^th August 2018

Intra-arterial phenargan is a known complication in 2 in 57575 cases. In a 2001 case, Delhis VIMHANS hospital and a doctor have been asked to pay Rs. 20 lakh as compensation on grounds of treatment offered to a 12-year-old boy, which led to the amputation of four fingers of his right hand on grounds of giving an intra-arterial injection of phenargan instead of an intravenous route.

What should have been the argument? According to the package insert, aspiration of dark blood does not preclude intra-arterial placement of the needle because blood can become discolored upon contact with promethazine.

Review of literature: Promethazine (Phenergan) injection is a commonly used product that possesses antihistamine, sedative, anti-motion sickness, and antiemetic effects. The drug is also a known vesicant which is highly caustic to the intima of blood vessels and surrounding tissue.

Formulated with phenol, promethazine has a pH between 4 and 5.5. Although deep intramuscular injection into a large muscle is the preferred parenteral route of administration, product labeling states that the drug may be given by slow IV push, which is how it is typically given in most hospitals.

However, due to the frequency of severe, tragic, local injuries after infiltration or inadvertent intra-arterial injection, Institute of Safe Medical Practices recommends that the FDA re-examine the product labeling and consider eliminating the IV route of administration.

Severe tissue damage can occur regardless of the route of parenteral administration, although intravenous and inadvertent intra-arterial or subcutaneous administration results in more significant complications, including: burning, erythema, pain, swelling, severe spasm of vessels, thrombophlebitis, venous thrombosis, phlebitis, nerve damage, paralysis, abscess, tissue necrosis, and gangrene. Sometimes surgical intervention has been required, including fasciotomy, skin graft and even amputation.

The true extent of this problem may be unknown. However, scores of reports suggest that patient harm may be occurring more frequently than recognized.

According to the package insert, “Proper IV administration of this product is well tolerated, but use of this route is not without some hazards.” To reduce the risk of these hazards, manufacturer labeling recommends to: give the drug in concentrations no greater than 25 mg/mL; administer the drug at a rate no greater than 25 mg/minute; inject the drug through the tubing of an infusion set that is running and known to be functioning satisfactorily; and to stop the injection immediately if the patient reports burning to evaluate possible arterial placement or perivascular extravasation.

How to use

1. Since 25 mg/mL is the highest concentration of promethazine that can be given IV, stock only this concentration (not the 50 mg/mL concentration).
2. Consider 6.25 to 12.5 mg of promethazine as the starting IV dose, especially for elderly patients.
3. Dilute the drug in 10 to 20 mL of normal saline if it will be administered via a running IV, or prepare the medication in minibags containing normal saline. Extravasation can also be recognized more quickly when promethazine is diluted than if the drug is given in a smaller volume.
4. Give the medication only through a large-bore vein (preferably via a central venous access site, but absolutely no hand or wrist veins). Check patency of the access site before administration. Note: according to the package insert, aspiration of dark blood does not preclude intra-arterial placement of the needle because blood can become discolored upon contact with promethazine. Use of syringes with rigid plungers or small bore needles might obscure typical arterial backflow if this is relied upon alone.
5. Administer IV promethazine through a running IV line at the port furthest from the patient’s vein. 
6. Administer IV promethazine over 10-15 minutes.
7. Before administration of the drug, tell patients to let you know immediately if burning or pain occurs during or after the injection.
8. Take consent
9. Build an alert that the drug is a vesicant and should be diluted and administered slowly through a running IV. 
10. Consider safer alternatives like ondansetron

Some cases

1. Necrosis caused by intra-arterial injection of promethazine: case report: Promethazine injections have led to necrosis and gangrene of the distal upper extremity when inadvertently injected into an artery. There have been few case reports of this alarming complication in the literature. We report on 2 cases of intra-arterial promethazine injection that led to amputation (Foret AL, et al. J Hand Surg Am. 2009 May-Jun;34(5):919-23).
2. Accidental intra-arterial injection of promethazine HCI during general anesthesia: Report of a case (Mostafavi H. Anesthesiology.1971;35:645).
3. Accidental intra-arterial injection: A case report, new treatment modalities, and a review of the literature (Keene JR, et al. J Oral Maxillofac Surg. 2006;64(6):965-8).
4. An unusual adverse event with the use of intravenous bolus of promethazine (Phenergan): The earlier used sedatives like promethazine, pethidine and pentazocine (Fortwin) are not commonly used these days but at times they are used especially in periphery for postoperative sedation and in gynecological surgeries and wards. We hereby report an unusual adverse event associated with the use of intravenous bolus of promethazine. With this case report we want to highlight that if promethazine is to be used for any purpose it should be given preferably intramuscular and if given intravenously, should be diluted and given slowly in a good running cannula. (However, patient inspite of receiving 20mg pethidine was anxious. For that 12.5mg of promethazine was given as slow IV push. Same dose of promethazine is repeated after 1hr intraoperatively. Rest of the intraoperative period was uneventful. No other drug was injected after promethazine. In the postoperative period, a bluish discoloration was noted on the dorsum of the hand in which the cannula was secured. And on touch the dorsum of the hand was cold). (Singh A, et al. Int J Res Med Sci. 2018 Jan;6(1):347-348).

The Delhi High Court has ruled that unsuccessful sterilization operation does not mean medical negligence, if the patient and her relatives were informed about chances of its failure. In the matter titled as “Lok Nayak Hospital versus Prema, RFA No. 56/2006” the Hon’ble High Court of Delhi vide judgment dated 06.08.2018 has held that medical negligence is not proved in case of unsuccessful sterilization operation, if the doctor / hospital has duly got the consent form and other forms signed by the patient and counter signed by her relatives in which it was specifically mentioned by the doctor / hospital that the operation need not be always successful and there are always some chances of failure, and if the operation is not successful the hospital or the concerned Doctor will not be held responsible.

Facts of the case

The respondent/plaintiff filed the subject suit by pleading that she was operated upon on 15.5.2001 in the appellant’s/defendant’s hospital by the concerned doctor namely Dr. Deepa. Respondent/plaintiff pleaded that she took all post-operative care including taking all prescribed medicines as also precaution but after a few months of the operation she suspected that she had conceived and therefore when she went to the Physical Health Centre at Dayalpur, Delhi, on 21.10.2002 and has got herself examined on 23.10.2002, it was discovered that respondent/plaintiff was pregnant as the tubectomy operation performed on her had failed. Respondent/plaintiff pleaded that Dr. Deepa (defendant no. 1 in the suit) fell short in taking reasonable and due care while performing the sterilization operation, resulting in defect and deficiency in the operation, therefore respondent/plaintiff became pregnant again to have her 7th child. After serving a legal notice/Ex. P-3 and which was replied to by the appellant/defendant no.2 vide reply dated 24.1.2003, Ex. P-2, the subject suit was filed.

The suit was contested by the appellant/defendant and it was denied that there was any negligence while performing the sterilization operation. The appellant/defendant pleaded that the respondent/plaintiff before performing her operation had signed two forms on 14.5.2001, and which forms were also counter-signed by the sister-in-law/Bhabhi of the respondent/plaintiff namely Ms. Suman, and that in these forms Ex. PW-1/D-1 and Ex. PW-1/D-2, it was specifically mentioned by the appellant/defendant that the operation need not be always successful and there are always some chances of failure, and if the operation is not successful the appellant/defendant or the concerned Doctor will not be held responsible. The contents of these documents were explained to the respondent/plaintiff in Hindi in the presence of her sister-in-law/Bhabhi, namely Ms. Suman. It was denied that the appellant’s/defendants doctors had given an assurance that the operation would be 100% successful. Appellant/defendant contended that the respondent/plaintiff was herself responsible because she could have got done the abortion in time, but she did not get such abortion done. The suit was therefore prayed to be dismissed.

The only relevant issue was issue no. 1 and the trial court has decided this issue in favour the respondent/plaintiff. Trial court has held that the respondent/plaintiff had not signed the forms Ex. PW1/D-1 and Ex. PW-1/D-2 inasmuch as she has specifically denied the signing of these forms by her and her sister-in-law/Bhabhi/Ms. Suman, and consequently, the trial court believed such stand of the respondent/plaintiff. Trial court has also held that since the concerned doctor namely Dr. Deepa, defendant no. 1 in the suit, did not depose and adverse inference has to be drawn against the appellant/defendant. Trial court has also observed that the signing of the forms Ex. PW1/D-1 and Ex. PW-1/D-2 by the respondent/plaintiff were not believable because the forms are dated 14.5.2001 and the operation was conducted on 15.5.2001. Trial court therefore held that the appellant/defendant was guilty of negligence in performing tubectomy operation which resulted in the birth of the respondent’s/plaintiffs 7th child, and therefore the suit was decreed for the sum of Rs. 2,20,000/-

Issue before the Hon’ble High Court

The only issue to be decided by the Hon’ble High Court was whether the trial court has rightly held that the appellant/defendant was guilty of negligence on account of the sterilization operation conducted on the respondent/plaintiff being unsuccessful.

Judgement of the Hon’ble High Court

8. Firstly, it is to be noted that the only allegation of negligence alleged by the respondent/plaintiff against the appellant/defendant is that the tubectomy/sterilization operation failed. Since medically there is never a 100% chance of success in sterilization operations, the mere fact that the operation was not successful, that by itself cannot be a reason to hold the appellant/defendant and its doctors guilty of negligence. This aspect is no longer res integra and is so held by a Division Bench of this Court in the case of Smt. Madhubala Vs. Govt. of NCT of Delhi, 118 (2005) DLT 515 (DB).
9. At this stage, I may note that the trial court has arrived at a completely perverse and illegal finding that the forms Ex. PW-1/D-1 and Ex. PW-1/D-2 do not bear the signatures of the respondent/plaintiff and her sister-in-law/Bhabhi/Ms. Suman and inasmuch simple denial by the respondent/plaintiff of her thumb impression on forms Ex. PW-1/D-1 and Ex. PW-1/D-2 and the signatures of her sister-in-law/Bhabhi/Ms. Suman is not enough because of various reasons. Firstly, signing of such forms is always and invariably got done by any private or public Hospital before a tubectomy/sterilization operation. Secondly, the documents Ex. PW1/D-1 and Ex. PW-1/D-2 contain the thumb impressions of the respondent/plaintiff and whereas a signature can be forged but thumb impressions can never be forged. Thirdly, admittedly, the name of the sister-in-law/Bhabhi of the respondent/plaintiff is Ms. Suman and how would the appellant/defendant have known the name of the sister-in-law/Bhabhi of the respondent/plaintiff as Ms. Suman and who has signed as her full name Suman on the two forms.Trial court therefore ought not to have believed the self-serving denial of the respondent/plaintiff of her thumb impression and signatures of her sister-in-law/Bhabhi/Ms. Suman on the forms Ex. PW-1/D-1 and Ex. PW-1/D-2.
10. In my opinion, the trial court has also unnecessarily laid emphasis on the defendant no. 1/Dr. Deepa in the suit for not appearing and deposing and therefore adverse inference has been drawn against the appellant/defendant, inasmuch as in my opinion there was no need of the defendant no. 1/Dr. Deepa to appear and depose inasmuch there was no specific case of negligence against the defendant no. 1/Dr. Deepa except that the operation was unsuccessful. Once the forms Ex. PW-1/D-1 and Ex. PW-1/D-2 are proved it cannot be argued by the respondent/plaintiff that there was 100% assurance given of the operation of being successful and which medically also is never 100% success.

Advisory

Dr KK Aggarwal and Ira Gupta

Before performing tubectomy/sterilization operation, every doctor and hospital should specifically inform the patient and her relatives that medically the said operation is not 100% successful. There should be an informed consent form, which specifically mentions that sterilization operations are not 100% successful and the same should be signed by the patient and her relatives (with their name). The thumb impressions of the patient and her relatives should also be taken as the same cannot be forged along with their signatures.

Alcohol consumption is responsible for 2.8 million deaths per year across the globe, with cancer the leading cause of alcohol-related death among people aged 50 years and older. There is no safe level of alcohol consumption. The findings come from the latest version of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), which analyzed data on 28 million people from 195 countries to estimate the prevalence of alcohol consumption, the amounts consumed, and the associated harms and published in the Lancet on August 23.

Rivaroxaban dosages for primary VTE prevention are lower (7.5 mg) than the currently recommended levels for reducing the post-discharge risk for recurrent VTE based on the EINSTEIN CHOICE trial.

A monoclonal antibody, previously known by its chemical name lanadelumab, has been FDA approved to treat patients with types I and II hereditary angioedema, a disease that affects about 1 in 50,000.

Faulty J&J hip implant, patients to get compensation. The Union health ministry will establish committees at the Central and state levels to track and compensate patients who received a faulty artificial hip implant that was recalled worldwide by the manufacturer Johnson & Johnson (J&J), in 2010. Close to 4,700 people with damaged hip joints in India received the implant before 2010, when it was recalled, of which only 1,080 were tracked and compensated. Of them, 275 underwent revision surgeries and the remaining are being closely monitored by their surgeons for side effects.

Following complaints from patients, the health ministry set up an 11-member committee on February 7, 2017, to investigate patient complaints of adverse events against J&J’s metal-on-metal Articular Surface Replacement (ASR) hip implant devices — XL Acetabular Hip System and Hip Resurfacing System. The committee was chaired by Dr Arun K Agarwal, former dean of Maulana Azad Medical College, and submitted its report on February 19, 2018. It said specialists must assess cases individually for treatment and compensation of at least Rs 20 lakh. Metal-on-metal hip implants have been largely discontinued because of the associated complications. With other implants, the revision surgery rate would be around 3-5%, but with this particular brand, it was a higher 10-12 percent (HT).

In view of extraordinary rise in prices of raw materials pushing up formulation prices significantly, pharmaceutical industry associations have urged the Central government to increase ceiling prices of drugs under National List of Essential Medicines (NLEM).

Watch and give your comments on this CPR video:  https://www.hotstar.com/tv/krishna-chali-london/s-1488/krishna-rebukes-prashant/1000217912

Video to watch: TEDx Talk

Dr KK Aggarwal: Modern day doctor-patient relationship

https://www.youtube.com/watch?v=i9ml1vKK2DQ

Dr KK Aggarwal

Padma Shri Awardee

President HCFI

Vice President CMAAO