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Year : 2015  |  Volume : 59  |  Issue : 12  |  Page : 823-825  

A simple test of baricity for subarachnoid drugs

Department of Anaesthesia, PGIMER and Associated Dr. RML Hospital, New Delhi, India

Date of Web Publication11-Dec-2015

Correspondence Address:
Jyoti Sharma
Room No. 324, Doctors Hostel, Dr. RML Hospital, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5049.171599

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How to cite this article:
Sharma J, Goila AK, Sood R. A simple test of baricity for subarachnoid drugs. Indian J Anaesth 2015;59:823-5

How to cite this URL:
Sharma J, Goila AK, Sood R. A simple test of baricity for subarachnoid drugs. Indian J Anaesth [serial online] 2015 [cited 2021 Jun 23];59:823-5. Available from: https://www.ijaweb.org/text.asp?2015/59/12/823/171599


Recently, during lumbar subarachnoid block with bupivacaine (heavy), we experienced problems such as delayed onset, early regression and patchy block. As clinicians we must be aware of the possible mechanisms for failure. There can be problems with lumbar puncture, errors in the preparation and injection of solution, inadequate spread of drugs through cerebrospinal fluid and failure of drug action on nervous tissue. [1],[2],[3],[4],[5]

On close scrutiny of the causes we found that 0.5% bupivacaine heavy (0.5% bupivacaine in 8% dextrose) supplied in the hospital formulary was from a different pharmaceutical company, which was not the usual supplier in our hospital. The drug formulation on the label was exactly the same as in other brands. Hence, we sent the drug for drug analysis by the government approved lab [Table 1], but we also decided to do an in vitro baricity test to compare the supplied drug with other brands available in the market. We tested the baricity of the following samples (1) bupivacaine plain 0.5% multi-dose vial (2) bupivacaine 0.5% heavy from manufacturer 'A', (3) bupivacaine 0.5% heavy from manufacturer 'B', (4) fentanyl 50 μg/ml, against cerebrospinal fluid (CSF). One millilitre clear autoclaved ampoules were used for our in vitro baricity test. We cleaned the surface of each ampoule and we colour labelled the drug to be tested with methylene blue. Four millilitres of each drug were added with one drop of methylene blue (0.1% w/v density 1.000) during its preparation.
Table 1: Report of drug analysis on 'form 39' from Government approved lab

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During the spinal subarachnoid block, before bupivacaine (heavy, unstained) was injected into the subarachnoid space, we collected 1 ml of CSF in each of the four ampoules; this volume was used as the in vitro test base solution against which baricity of the test drug was to be compared.

After the collection of CSF in each ampoule, 0.2 ml of dye labelled test drug was put on the surface of CSF in the test tubes marked 'isobaric'(I), heavy brand X (HX), heavy brand Y (HY) and fentanyl (F). We observed the pattern of distribution of drug-coloured with methylene blue for 30 min. Four colour labelled drugs (stained drugs SDR) were thus obtained: SDR I, SDR HX, SDR HY and SDR F.

It was observed that test tube containing SDR 'I' had homogenous distribution of SDR into the CSF showing that SDR 'I' was isobaric [Figure 1]a-c. Both SDR 'HX' and 'HY' settled to the bottom of the CSF in the test tubes proving they are hyperbaric although the time taken to settle at the bottom was more with 'HY' than 'HX' (15 min vs. 30 min) [Figure 1]a-c. SDR 'F' formed a superficial layer at top of the test tube indicating it was hypobaric [Figure 1]a-c. We observed that the drug from one manufacturer settled finally to the bottom within 15 min versus 30 min taken by the drug from other manufacturer.
Figure 1: (a) Effect of the test drug on base solution at 5 min, (b) Effect of the test drugs on base solution after 15 min, (c) Effect of the test drug on base solution after 30 min

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Thus, we observed that at room temperature, SDR 'I' (from multi-dose vial bupivacaine) is isobaric (with no hint of hyperbaricity (settling at the bottom) or hypobaricity (forming a scum at the surface)). SDR 'HX' started settling at 5 min and settled finally at the bottom within 15 min; the time taken by SDR 'HY' was 30 min. for final settling. The fentanyl was clearly a hypobaric drug forming a scum at the surface.

As the test reports show, sample 'A' (sample HX) of the test drug had dextrose concentration of 76.9 mg/ml equivalent to calculated density of 1.023279. Sample 'B' (sample HY) had a dextrose concentration of 75.9 mg/ml equivalent to calculated density of 1.022969. This is, compared to an ideal solution of bupivacaine 0.5% with dextrose 80 mg/ml, which has a density of 1.02424 at 37°C. [6]

The densities of 0.5% bupivacaine with values lower than 8% dextrose at 37°C were calculated using the data given in the study by McLeod. [6] The corresponding densities at different dextrose concentrations were calculated by using the formula y = mx + c for 0.5% bupivacaine with dextrose at 37°C, slope as 3.10 × 10 -4 , c (intercept) as 0.99944 and coefficient of correlation R2 as 0.99 [Graph 1]. Although changes in density may seem minimal and clinically unnecessary, a change in density as low as 0.0006 mg/ml of 0.5% bupivacaine heavy may influence the spread of local anaesthetic into the CSF. [7]

We inferred that the difference in time taken by drugs 'HX' and 'HY' for settling at the bottom is an indication of different specific gravity of the drugs from two manufacturers indicating an error in formulations as to the presence of glucose.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Hocking G, Wildsmith JA. Intrathecal drug spread. Review article. Br J Anaesth 2004; 93:568-78.  Back to cited text no. 1
Catterall WA, Mackie K. Local anesthetics. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 12 th ed. Ch. 14. 565-582 2008.  Back to cited text no. 2
Cousins MJ, Bridenbaugh PO, editors. Neural Blockade in Clinical Anesthesia and Management of Pain. 3 rd ed. Philadelphia: Lippincott-Raven; 1998.  Back to cited text no. 3
Fettes PD, Jansson JR, Wildsmith JA. Failed spinal anaesthesia: Mechanisms, management, and prevention. Br J Anaesth 2009;102:739-48.  Back to cited text no. 4
Logan MR, McClure JH, Wildsmith JA. Plain bupivacaine: An unpredictable spinal anaesthetic agent. Br J Anaesth 1986;58:292-6.  Back to cited text no. 5
McLeod GA. Density of spinal anaesthetic solutions of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose. Br J Anaesth 2004;92:547-51.  Back to cited text no. 6
Stienstra R, Gielen M, Kroon JW, Van Poorten F. The influence of temperature and speed of injection on the distribution of a solution containing bupivacaine and methylene blue in a spinal canal model. Reg Anesth 1990;15:6-11.  Back to cited text no. 7


  [Figure 1]

  [Table 1]


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