ANESTH ANALG
`2000;91:1306–13
`
`LETTERS TO THE EDITOR
`
`1307
`
`I have measured the Fip N2O in 50 laparoscopic gynecology,
`intraperitoneal hernia repair and cholecystectomy patients. The Fet
`N2O was 65%–70%, the duration of cases from 20 min to 3 h.
`At case end, a sterile tubing was connected to the trocar stopcock
`before deflation of peritoneal gas. The tubing was then connected to
`a standard end-tidal gas monitor. Peritoneal gas was sampled for
`approximately 60 s, at which time a stable reading had been
`achieved.
`The smallest Fip N2O observed was 1%–2%, the largest was
`9%–10%. Small numbers were associated with shorter cases, large
`numbers with longer cases. The Fip N2O never exceed 10%, a
`concentration that does not facilitate combustion. Bowel lumen N2O
`was not measured and would require a different methodology.
`The difference between observations in the pig model and clinical
`patients may be by a “washout” effect on the increase of Fip N2O
`caused by the loss of insufflating CO2 around additional trocar
`incisions used in patients. The seal around the trocar in the pig
`experiment may have been airtight. It is a common observation that
`large quantities of insufflating CO2 are required in patient cases to
`replace lost CO2. Interested parties can easily duplicate my study in
`the clinical patient setting. All that is required is a sterile IV exten-
`sion tubing and 60 s of time. If Fip N2O concentrations stay at or
`below the 10% level during cases of 3 h, perhaps N2O ought not be
`abandoned.
`Those who advocate abandonment of N2O usually advocate use
`of 100% O2. This same methodology could easily be used to measure
`the intraperitoneal concentration of O2, a gas that supports combus-
`tion at roughly one-half the concentration that does N2O and might
`increase the risk of combustion rather than decrease it.
`Clair S. Weenig, MD
`University of California San Francisco
`San Francisco, CA
`Reference
`1. Diemunsch PA, Torp KD, Van Dorsselaer T, et al. Nitrous oxide fraction in the carbon
`dioxide pneumoperitoneum during laparoscopy under general inhaled anesthesia in
`pigs. Anesth Analg 2000;90:951–3.
`In Response:
`As stated in our article (1), the aim of our study was to establish the
`time course of the N2O pollution in a CO2 pneumoperitoneum. This
`was done under precise experimental conditions, i.e., a 9-h pneu-
`moperitoneum without external leaks and provision of fresh CO2
`from the insufflator limited to the amount needed to compensate for
`peritoneal gas resorption, i.e., 3.5 6 0.8 L/h, to maintain an intra-
`peritoneal pressure of 12 mm Hg.
`It seems unlikely that these experimental conditions, in which Fip
`N2O ultimately approaches Fet N2O, could be met in a usual clinical
`situation. Conversely, as shown by Neuman et al. (2), time periods
`with no external leaks from the pneumoperitoneum can occur and
`last long enough for the Fip N2O to reach values above 30%, which
`may support combustion of bowel gases.
`Even in the presence of such Fip N2O, the risk of fire is fortunately
`small because a bowel perforation has to occur to allow H2 and/or
`methane to reach the pneumoperitoneum. Indeed, the flammable
`colonic gases cross the intact bowel barrier poorly. Hunter et al. (3)
`could not detect methane and found hydrogen in very small
`amounts (0.016% to 0.075%) in the pneumoperitoneum during lapa-
`roscopic procedures lasting 30 min to 2 h. Similarly, in our experi-
`mental model, H2 and O2 were found as traces only (one search
`every 10 min during 9 h after the peritoneal insufflation).
`The simultaneous occurrence of 1) a high Fip N2O, 2) a bowel
`perforation, and 3) an electric spark, certainly represents an unlikely
`event (because of the relative scarcity of the two first points), but the
`risk is not nil. More important may be the risk for a N2O-containing
`CO2 pneumoperitoneum to worsen the consequences of a gas em-
`bolization. We are currently working on this subject.
`Avoidance of N2O pollution in the CO2 pneumoperitoneum could
`be achieved by giving anesthesia without N2O. However, the solu-
`tion we suggest for a constant N2O-free pneumoperitoneum is to set
`up a constant pneumoperitoneal leak whose continuous compensa-
`tion by fresh CO2 from insufflator to maintain the pre-set pressure;
`this would prevent any significant N2O accumulation. The two
`questions related to this solution are the definition of a significant
`
`Fip N2O and the flow of the leak necessary to avoid such a Fip N2O.
`Preliminary results indicate that a leak of 24 L/hour is enough to
`maintain Fip N2O less than 10%.
`Most laparoscopic procedures are performed by using a much
`higher total pneumoperitoneal turnover, and the usual total gas
`output from the insufflator in our clinical conditions can range from
`100 to 300 L/hour. This washout is neither steady nor constant. It
`occurs mainly during limited periods of time, essentially when the
`surgeon moves instruments in and out through the trocars, or
`during the extraction of surgical samples. All maneuvers of this
`kind cause the gas-tight septa of the trocars to open. Leaks around
`the trocars are less important in our practice. Between these high-
`flow washout periods, other phases without leaks may occur and
`promote N2O accumulation. In the Neuman et al. (2) series (19
`female patients), when no external leak occurs, Fip N2O reaches
`19.9% 6 4.8%, 30.3% 6 6.8%, and 36.1% 6 6.9% after 10 min, 20 min,
`and 30 min, respectively. This means that during the course of a
`laparoscopic procedure, the Fip N2O may increase relatively fast
`and evolves alternately with the washout phases. One sole mea-
`surement at the end of the procedure may conceal the possible
`“peaks and valleys” in Fip N2O and does not reflect the associated
`risk periods that may have occurred during the surgery. However,
`short procedures (20 min in all) may not allow a gas-tight pneumo-
`peritoneum time enough to enable the Fip N2O to rise.
`For all the above mentioned reasons, we advocate the setting of a
`constant and measured pneumoperitoneal
`leak rather than the
`abandonment of the N2O as part of the anesthesia and lung venti-
`lation with oxygen-enriched air. Some surgeons open one of the
`trocar stopcocks from time to time or even leave it open all the time
`for the smoke from electrocautery to be vented. This unmeasured
`venting may also prevent N2O accumulation, but it is unpredictable
`and, according to our recent experiments, seems much too impor-
`tant for the aimed objectives. A much oversized gas turnover
`unduly increases the heat
`loss associated with laparoscopic
`procedures.
`Finally, our end-tidal gas monitors based on infrared technology
`are not efficient enough to perform the above-mentioned mea-
`surement, i.e., to provide simultaneous readings of CO2, N2O, O2,
`CH4 and H2 in a range of concentrations from 0% to 100% (the initial
`value of Fip CO2). The devices used in the literature for similar
`protocols are mass spectrometers, alone or coupled with a gas
`chromatograph as in our study. For our research protocols in
`progress, we are currently using a micro gas chromatograph, allow-
`ing reliable constant monitoring of the pneumoperitoneum compo-
`sition in the operating theater, just as the end-tidal gas monitor does
`for the respiratory gas mixture.
`Pierre A. Diemunsch, MD
`Sidiki Doumbia, MD
`Joe¨l Leroy, MD
`Hoˆpitaux Universitaires de Strasbourg
`67000 Strasbourg, France
`
`References
`1. Diemunsch PA, Torp K, Van Dorsselaer, T et al. Nitrous oxyde fraction in the carbon
`dioxide pneumoperitoneum during laparoscopy under general inhaled anesthesia in
`pigs. Anesth Analg 2000;90:951–3.
`2. Neuman GG, Sidebotham G, Negoianu E, et al. Laparoscopy explosion hazards with
`nitrous oxide. Anesthesiology 1993;78:857–9.
`3. Hunter JG, Staheli J, Oddsdottir M, et al. Nitrous oxide pneumoperitoneum revisited:
`is there a risk of combustion? Surg Endosc 1995;9:501–4.
`
`Any Propofol Compatibility Study Must
`Include an Emulsion Stability Analysis
`
`To the Editor:
`We would like to comment on the recent technical communication
`by Stewart et al. (1) concerning the stability of a propofol and
`remifentanil admixture. Any stability study involving emulsions
`must address not only the chemical stability of the constituent drugs
`as determined by high-performance
`liquid chromatography
`(HPLC), but also the stability of the emulsion vehicle itself before
`
`Fresenius Ex. 2007
`Bass et al. v. Fresenius Kabi USA, IPR2016-00254
`
`

`
`1308
`
`LETTERS TO THE EDITOR
`
`ANESTH ANALG
`2000;91:1306–13
`
`the mixture can be considered safe for clinical use. Any change in
`the emulsion particle size resulting from admixing propofol may
`have adverse consequences for patient safety. Fat emulsion particles
`large enough to cause fat emboli may not be visible to the unaided
`eye. Laser diffraction and optical microscopy particle size analysis,
`such as that published by Prankerd and Jones (2) concerning the
`propofol/thiopental mixture must be performed before using any
`propofol admixture.
`We would also question the authors’ statement that the propofol/
`remifentanil mixture is safe to store for 36 hours. It is well docu-
`mented that propofol’s fat emulsion vehicle is an excellent medium
`for microbial growth (3,4). Studies similar to those conducted with
`the thiopental/propofol mixture, which have documented that
`combinations antimicrobial activity because of its high pH (5), need
`to be performed. However, there is nothing in the physiochemical
`nature of the remifentanil/propofol mixture that would appear to
`confer similar antimicrobial properties. Until microbiological and
`emulsion stability studies are performed, a propofol/remifentanil
`mixture cannot be assumed to be safe for storage or for administra-
`tion to patients.
`Eric L. Chernin, RPh*
`Barry Smiler, MD†
`Departments of *Pharmaceutical Care Services and †Anesthesia
`Sarasota Memorial Hospital
`Sarasota, Florida 34239
`
`Drs. Stewart et al. did not wish to respond to this letter.
`
`References
`1. Stewart JT, Warren FW, Maddox FC, et al. The stability of remifentanil hydrochloride
`and propofol in polypropylene syringes and polyvinyl chloride bags at 22°–24°C.
`Anesth Analg 2000;90:1450–1.
`2. Prankerd RJ, Jones RD. Physiochemical compatibility of propofol with thiopental
`sodium. Am J Hosp Pharm 1996;53:2606–10.
`3. Carr S, Waterman S, Rutherford G, et al. Postoperative infections associated with an
`extrinsically contaminated intravenous anesthetic agent.
`4. Bennett SN, McNeil MM, Bland LA, et al. Postoperative infections traced to contam-
`ination of an intravenous anesthetic, propofol. NEJM 1995;333:147–54.
`5. Crowther J, Hrazdil J, Jolly DT, et al. Growth of microorganisms in propofol, thiopen-
`tal, and in a 1:1 mixture of propofol and thiopental. Anesth Analg 1996;82:475–8.
`
`Coffee Is Not a Clear Liquid
`To the Editor:
`I read with interest the recent survey of the practice policies of
`anesthesiologists regarding the intake of clear liquids and a light
`breakfast by adult patients presenting for elective outpatient sur-
`gery (1). However, I was puzzled by the authors’ statement: “. . .cof-
`fee and tea are included as clear liquids. . .” (1).
`Shevde and Trivedi considered black coffee a clear liquid in their
`study of the effects of clear liquids on gastric volume and pH (2).
`They stated: “We have used the word ‘clear’ to exclude liquids with
`suspensions (such as juice with pulp) or those that may form solids
`in the stomach such as milk” (2). Shevde and Trivedi evidently did
`not consider coffee with milk to be a clear liquid.
`An obvious fact is that coffee is not a clear liquid. Indeed, a test of
`several types of coffee contained in clear cups demonstrated the
`opacity of the liquids both before and after the administration of
`sugar and milk or cream.
`I propose that authors should state explicitly if they mean that, in
`their judgment, coffee whether with milk or cream or black may be
`safely included with plain tea and other obviously clear liquids as a
`beverage that patients may safely consume before elective outpa-
`tient surgery. However, that would still not make coffee a clear
`liquid.
`My reason for raising this apparently trivial point is that, as an
`anesthesiologist who works at several facilities dealing with outpa-
`tients, this issue has come up more than once, and it has been a
`source of confusion to health care professionals and patients.
`Mitchel B. Sosis, MD, PhD
`Department of Anesthesiology
`Campus Eye Group
`Trenton, New Jersey
`
`References
`1. Pandit SK, Loberg KW, Pandit UA. Toast and tea before elective surgery? A national
`survey of current practice. Anesth Analg 2000;90:1348–51.
`2. Shevde K, Trivedi N. Effects of clear liquids on gastric volume and pH in healthy
`volunteers. Anesth Analg 1991;72:528–31.
`
`In Response:
`We greatly appreciate Dr. Sosis’s interest in our paper (1). This also
`gives us an opportunity to clarify the prevalent ambiguity about
`types of “clear” liquid that are allowed 2–3 h before elective surgery.
`Dr. Sosis has asked a very relevant question: is coffee (or tea) a clear
`liquid? According to the Webster’s dictionary, the word “clear”
`(adjective) has many meanings. Some of these are, bright, luminous,
`obvious, plain, cloudless, free from blemishes, free from impurity,
`transparent, and free from doubt.
`Dr. Sosis has interpreted “clear” as “transparent” or colorless,
`something that we can see through, e.g., water, transparent glass, a
`noncola drink (such as 7-Up). According to this interpretation, black
`coffee, plain tea, pulp-free orange juice, some types of apple juice,
`and cola drinks may not be accepted as “clear” liquid. However, if
`one takes the other meaning of “clear,” that is, free from blemishes
`or particulates, then all of the above liquids are actually “clear.”
`Milk, however, is not a clear liquid, because it forms curd (solid
`particulate material) as soon as it reaches the stomach. So, adding
`milk or cream to coffee makes it “unclear.”
`We have taken an informal poll among the members of our
`department, and almost everyone agreed that black coffee and black
`tea are examples of clear liquid.
`Reviewing the published literature, we find that several authors
`have studied the implications of ingestion of black coffee before
`elective surgery. Hutchinson et al. (2) and Maltby et al. (3) found
`that neither the residual gastric volume nor the gastric acidity is
`increased after ingestion of black coffee (150 mL) or pulp-free or-
`ange juice (150 mL) 2–3 h before surgery, with or without ranitidine.
`Both concluded black coffee and pulp-free orange juice may be
`safely allowed 2–3 h before the induction of general anesthesia.
`Shevde and Trivedi (4) gave 240 mL of water, pulp-free orange juice,
`or black coffee to volunteers and found all volunteers had a gastric
`volume less than 25 mL with a slight decrease in pH within 2 h of
`orally taking one of the three 240-mL liquids. They concluded that
`ingestion of (any of the three) clear liquids (water, pulp-free orange
`juice, or black coffee) 2 h before general anesthesia is safe.
`In summary, it is clear to us, as it is to a majority of practicing
`anesthesiologists in North America, that black coffee, black tea,
`apple juice, pulp-free orange juice, cola drinks, and of course, water
`are examples of clear liquid that could be allowed 2–3 h before
`elective surgery.
`Finally, we would strongly suggest that the title of this correspon-
`dence that Dr. Sosis has supplied, “Coffee is Not a Clear Liquid,” is
`inappropriate, because it sounds like a conclusion. It is not; at best,
`it is controversial. By looking at the title, a casual reader will get a
`wrong impression about the controversy. So, we would suggest a
`title: “Is Coffee a Clear Liquid?”
`Sujit K. Pandit, MD
`Katherine W. Loberg, BS
`Uma A. Pandit, MD
`Department of Anesthesiology
`University of Michigan Health Care System
`Ann Arbor, MI 48109
`
`References
`1. Pandit SK, Loberg KW, Pandit UA. Toast and tea before elective surgery? A National
`survey on current practice. Anesth Analg 2000;90:1348–51.
`2. Hutchinson A, Maltby JR, Reid CR. Gastric volume and pH in elective inpatients. Part
`I. Coffee or orange juice versus overnight fast. Can J Anaesth 1988;35:12–5.
`3. Maltby JR, Reid CR. Gastric volume and pH in elective inpatients. Part II. Coffee or
`orange juice with ranitidine. Can J Anaesth 1988;35:16–9.
`4. Shevde K, Trivedi N. Effects of clear liquids on gastric volume and pH in healthy
`volunteers. Anesth Analg 1991;72:528–31.
`
`Fresenius Ex. 2007
`Bass et al. v. Fresenius Kabi USA, IPR2016-00254