MEDICAL GASES: REGULATION AND USE
(Anoop Paruchuri, Y. Achyuth, P. K. Manna and Guru Prasad Mohanta*
Department of Pharmacy Practice, Annamalai University, Annamalai Nagar – 608 002
*E. Mail: )
Medical gases are those which aremanufactured, packaged, and intended for administration to a patient in anesthesia, therapy, or diagnosis. The officially listed therapeutic gases include Oxygen, Helium, Carbon dioxide, Nitrous oxide, Medical air and Nitrogen. These gases are usually given to the pre operated, intra operated and post operated patients and to the patients in case of emergency. These gases are to be supplied in airtight, color coded, well labeled container as required by the respective regulatory authorities of every country or via a central line which runs thru the entire hospital.In spite of all the regulations, precautions put down by the regulatory authorities, there are still reports of medical gas mix ups which even resulted in death of the patients. Even though the mistake done is not intentional it puts the patient’s life at jeopardy. So, eventually who is to be blamed for the mix up, the regulatory authority, the manufacturer, the distributor, the physician or the nurse? Well it is a rhetorical question which still remains unanswered.These reports emphasize the need of regular monitoring from their manufacture until their administration.
Oxygen, Helium, Carbon dioxide, Nitrous oxide, Medical air and Nitrogen are treated as medical or therapeutic gases(2, 3, 4).
MEDICAL OXYGEN (1, 2, 3, 4) Listed in U.S.P. 31, I.P. 2007, Eur. P, China, Japan and Viet.
Fig.1 Oxygen Cylinder Fig.2 labeling of the cylinder Fig.3 Warning statement
The normal air contains 21% of oxygen with a partial pressure of 21kpa at sea level. The inhaled oxygen then enters the alveoli where it dissolves in to the blood and combines with Hemoglobin. Decrease in the partial pressure of Oxygen which happens at high altitudes or presence of any disease statesaffect the dissolution rate of Oxygen leading to Hypoxia (7, 8). Usually oxygen therapy is given by inhalation to correct hypoxemia and in conditions causing respiratory failure and also in conditions where the oxygen content of the air breathed is inadequate such as high altitude disorders. Oxygen is of value in the treatment of poisoning with a number of substances, including carbon monoxide, cyanides, and dichloromethane. It provides enhanced oxygenation in inhalation injury.
Use and Administration:
Oxygen is usually supplied in gas cylinders from which the administration to the patient is done by using a facial mask which can hold about 60% oxygen or through tight fitting anesthetic type mask that can hold up to 100% oxygen. 28-40% oxygen is usually used in treatment of C.O.P.D. and 40-60% is used in case of bronchial asthma and 100% oxygen is usually used in treatment of severe hypoxia and noxious gas poisoning. Usual rate of administration is around 1-15 L/min (7, 8).
“Hyperbaric Oxygen therapy” is the administration of 100% oxygen at 1atm pressure for cases like myocardial infraction, cluster headache, stroke and cancer(10). It is widely used in emergencies.
Respiratory system is the first to be effected by continuous supply of oxygen for more than 15 hours. Reterolentalhyplasis occurs in children. The symptoms of C.N.S. occur only above the partial pressure of 200atm of Oxygen which causes seizures, temporary blindness. It is not contraindicated in pregnancy and lactation (7, 8, and 10).
MEDICAL CARBON DIOXIDE(2, 3. 4, 7, 8): Listed in Eur.P, USP 31 and China. P
Fig.4 Carbon dioxide cylinder
It is the product of metabolism in the body. It is usually formed in the cells, it rapidly diffuses from the tissues into the blood and it is exhaled form lungs. Decrease in the concentration of C02 in the blood is called as “Hypocarbia” which is manifested by decrease in blood pressure, vasoconstriction of skin, intestine and kidney. “Hypercarbia” is associated with an increase in the concentration of CO2 in the blood and is manifested by increased blood pressure, depression of cerebral cortex, increase in the pain threshold level and cardiac arrythmiasis.
Uses and Administration:
Inhalation of CO2 is used less commonly today than in the past because there are now more effective treatments for most indications. Inhalation of carbon dioxide has been used during anesthesia to increase the speed of induction and emergence from inhalational anesthesia by increasing minute ventilation and cerebral blood flow (7, 8). It is also used in endoscopic procedures. Carbonated preparations are used for unmasking the unpleasant taste of medicinal preparations and used in the treatment of warts in the form of dry ice.Carbon dioxide is usually administered through the lungs by inhalation. The major exceptions are when a metered supply is fed into the oxygenator of an extracorporeal circulation of a cardio-pulmonary by-pass system, and when the gas is used for laparoscopic surgery (10).
CO2 is contra indicated in metabolic acidosis. Above a concentration of 6%, carbon dioxide causes headache, dizziness, confusion, palpitations, hypertension, dyspnoea, increased depth and rate of respiration, and CNS depression(7, 8, 10). Concentrations of about 20% and higher produce convulsions and loss of consciousness; inhalation of 50% carbon dioxide is reported to produce central effects similar to anesthetics. The inhalation of high concentrations may produce respiratory acidosis. Abrupt withdrawal of carbon dioxide after prolonged inhalation commonly produces pallor, hypotension, dizziness, severe headache, and nausea or vomiting.Carbon dioxide interacts with anesthetic agents when the concentration is raised and gives rise to cardiac dysrhythmias(7, 8, 10). Carbon dioxide, by altering the pH influences the uptake, distribution and action of many drugs including neuromuscular blocking agents, and hypotensive agents. Carbon dioxide interacts with adrenergic substances such as adrenaline. The use of CO2along with adrenaline is strictlycontraindicated. CO2 is not recommended in pregnancy but advised during lactation (10).
MEDICAL NITROGEN(2, 3, 4): Listed in USNF 26. Eur.P and Jap P.
It is a colorless odorless gas and does not support combustion.
Use and Administration:
Nitrogen is used as a diluent for pure oxygen or other active gases and as an inert gas to replace air in containers holding oxidisable substances. Liquid nitrogen is used as a cryotherapeuticagent for the removal of warts and for preservation of tissues and organisms. Generally it is used along with Helium and Oxygen(10). A combination of 9% Helium, 35% Oxygen and remaining with Nitrogen is used as a medical gas mixture for pulmonary physiology.
No contra indications were reported but it is not advisable for use in the elderly for the treatment of bronchitis. Nitrogen narcosis has been reported after the use of gas in high pressure atmospheres like deep diving (7).
MEDICAL HELIUM(2, 3,13, 14): Listed in Eur. P 6.2 and USP 32
It is a colourless gas which is not combustible and it does not support combustion.
Use and Administration:
Helium is generally used along with 21% or more of Oxygen in a mixture called “HELIOX”. The mixture is used by low depth divers as the problem of Nitrogen narcosis is avoided my using the mixture. It is also used in pulmonary function testing, in treatment of respiratory obstruction, and as a label in imaging studies. It is usually administered by using a face mask or an endotracheal tube (10, 13, 14).
Symptoms of asphyxiation include rapid and gasping respiration, rapid fatigue, nausea and vomiting and cyanosis, and may lead to loss of consciousness and death from anoxia.Inhalation of helium for a longer period is found to increase the vocal pitch and causes voice distortion. Cerebral artery gas embolism has been reported after inhalation of helium from a pressurized container. It is not contraindicated in pregnancy and lactation.
MEDICAL NITRIC OXIDE(1, 2, 3, 4, 10): Listed in I.P 2007, USP 31, Eur. P and Jap P.
Fig. 5 Nitric oxide cylinder Fig. 6 Labeling on the cylinder Fig. 7 Cylinder connected to a central line
It is found exogenously as an air pollutant and a toxin but it is also found endogenously as a vasodilator. The endogenous NO is produced from L-arginine by a family of enzymes called NO synthases. It is an endogenous chemical messenger.
Use and Administration:
Nitrous oxide is used when an inhalation anesthetic is required. The administration of nitrous oxide is usually accompanied by simultaneous administration of a volatile agent such as halothane, ethane, etc.(5, 6). In the relief of severe pain, usually in emergency situations, it is used along 50% oxygen in short-term procedures which inevitably involve pain, such as wound and burn dressing, wound debridement and suturing. It is administrated usually with 50% oxygen in dental work to provide short-term analgesia for tooth extraction and other brief procedures, administered with 50% oxygen occasionally as an insufflating agent in laparoscopy in cryosurgery as a refrigerant. Nitrous oxide is administered through a face mask or tracheal tube by means of an anesthetic apparatus. The gas is breathed in by the patient and absorbed through the lungs. In an average adult, nitrous oxide is administered by inhalation through a suitable anesthetic apparatus in concentrations up to 80% with oxygen as the balance. Nitrous oxide is more useful in the elderly and the depressant effects of added agents are reduced (6). Nitrous oxide is strongly recommended in the anesthesia of neonates in obstetrical anesthesia. The nitrous oxide level is kept below 70% to allow a substantial oxygen level to be provided. Nitrous oxide plays a major role because injected agents depress the breathing of the infant and volatile agents depress uterine contraction as a general rule, the more ill the patient, the more susceptible is the patient to other anesthetic agents and the more nitrous oxide is relied upon.
Nitrous oxide should not be used for more than a total of 24 hours, or more frequently than every 4 days, without close clinical supervision and hematological monitoring. Nitrous oxide causes inactivation of vitamin B12, which is a co-factor of methioninesynthase(5,6).Folate metabolism is consequently interfered and DNA synthesis is impaired following prolonged administration of nitrous oxide. Prolonged or frequent use of nitrous oxide may result in megaloblasticbone marrow changes, myeloneuropathyand sub-acute combined degeneration of the spinal cord.Reduced fertility in healthcare personnel has been reported where they have beenrepeatedly exposed to high levels of nitrous oxide above the specified occupational exposure limits in inadequately ventilated rooms(7).Acute discontinuation of NO inhalation can lead to a rebound pulmonary artery hypertension with an increase in right-to-left intrapulmonary shunting and a decrease in oxygenation. To avoid this phenomenon, a graded decrease of inhaled NO concentration is used in weaning a patient from inhaled NO.
MEDICAL AIR(2, 3, 4): Listed in USP 31, Eur. P, B.P 2008. Chin, Jap, Viet.
Fig. 8 Medical air plant
It is a natural or synthetic mixture of gases consisting largely of nitrogen and oxygen. It contains not less than 19.5% and not more than 23.5% of oxygen.The mixture is also available in 50:50 ratios which are pressurized to 15000 kpa at 200C.
Specification of medical air(12)
Medical grade air should be free from toxic products, flammable or toxic vapors, and odor’s at all points in the pipeline system. Although it is not sterile medical grade air is clean and at STP(standard temperature and pressure) should not contain more than:
- 0.5mg of particulate oil mist /cubic meter of air;
- 5.5mg of carbon monoxide/ cubic meter of air;
- 900 mg carbon dioxide/ cubic meter of air;
- No moisture; and
- No bacterial contamination.
Surgical instruments require compressed air at 7.2bars or 105psi.
Anesthetic ventilators require compressed air at 4.1 bars or 60psi.
Use and Administration(7):
The medical air is usually administered through the lungs by inhalation usually through volumetric metering and absorption analysis devices. It may be administered by means of a tent.It can also be administered via a central line which originates at the medical air plant and terminates into small branches. These branches connect to the mask where the air is administered to the patient. It is generally used in pulmonary function test, hyperbaric oxygen therapy and in the treatment of Hypoxia.
No adverse effects and contraindications were reported but prolonged use of the mixture may result in Oxygen toxicity. It is not contraindicated in pregnancy and lactation (10).
COUNTRYAUTHORITIES RESPONSIBLE FOR REGULATION OF MEDICAL GASESINDIA / U.S.A / U.K
The Authority / Ministry of Commerce and Industry(24). Drugs Control Authority of State. / F.D.A/ C.D.E.R(23)
The Act / Explosives act 1884/ Gas cylinder rules 2004.
Drugs and Cosmetics Act / Federal Food and Drug Cosmetics act/Compressed medical gas guideline 1989 / Medicines Act 1968.
Official listing of the country / Indian Pharmacopeia / U.S.P, U.S.P-N.F / B.P, Eur. Pharmacopeia
Above are the respective authorities responsible for regulating and monitoring the use of medical gases in India, U.S.A and United Kingdom. The guidelines developed by the authorities are based on the acts governingthe respective countries
COLOUR CODING OF THE CYLINDERS:
Indian Pharmacopeia defines a gas cylinder as a “Metallic container designed to hold a gas under pressure” (1). The cylinders are required to be colour coded for easy identification andavoid accidental mix ups.STANDARD NAME / INDIA(I.P 2007) / USA(USP 31) / UK (B.P 2008)
Medical Air / - / Yellow / White
Medical Oxygen / Shoulder white and remainder in black / Green / Shoulder white and remainder in black
Medical Nitrogen / - / Blue / Shoulder black and remainder in grey
Medical Helium / - / Black / Brown
Medical Carbon dioxide / - / Grey / Grey
Medical Nitrous oxide / Blue / Blue / Blue
Every authority recommends that the cylinder should have the name of the gas and its symbol stenciled across the shoulder of the cylinder and it must be clearly visible. The authority also insists the “WARNING” statement to be published on the cylinder.
The USFDA guideline on warning statement on the cylinder (9, 11,): “Warning—Administration of (name of gas) may be hazardous or contraindicated. For use only by or under the supervision of a licensed practitioner who is experienced in the use and administration of (name of gas) and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken.”
MEDICAL GAS MIX UPS ACROSS THE WORLD IN THE LAST DECADE
This is a brief report of medical gas mix ups that occurred across the world in the 10-15 years.S.NO / COUNTRY / YEAR / MIX-UP / OUTCOME
1 / USA(15) / 1996 / Improper cleaning of gas cylinders that are converted from industrial to medical use / Several patients experienced respiratory problems
2 / USA(15) / 1996 / Carbon dioxide instead of Oxygen / 7 children had respiratory distress
3 / USA(15) / 1997 / Argon instead of Oxygen / Burning eyes and respiratory problems
4 / USA(15) / 1998 / The oxygen cylinder contained traces of Chlorine / Death
5 / USA(15) / 1998 / Nitrogen instead of Oxygen / Death
6 / USA(15) / 1999 / Carbon dioxide instead of Oxygen / Death to 7 patients
9 / USA(15) / 2000 / Nitrogen instead of Oxygen / Death to a 3 year old female child
10 / England(18) / 2001 / Nitrous Oxide instead of Oxygen / Death due to hypoxia and asphyxia
11 / England(19) / 2006 / Nitrous Oxide instead of Oxygen / Respiratory distress
12 / USA(16) / 2009 / Nitrous Oxide instead of Oxygen / Death to 7 patients
13 / Italy(17) / 2010 / Laughing gas instead of Oxygen / Coma
14 / India(21) / 2011 / Nitrous Oxide instead of Oxygen / Coma
15 / USA(20) / 2011 / Nitrous Oxide instead of Oxygen / Brain damage
BRIEFING ON MEDICAL GAS TRAGEDIES:
Trial Begins In Medical Gas Mix-up- 5/6/2010(17)
Themedical gasmix-up in a Castellaneta, Italy,and hospital is beckoning medicalgasproviders and handlers to review proper procedures. Eight heart patients in the Southern Italy hospital were mistakenly givenlaughing gasinstead ofoxygen. Thirty individuals, including staff and executives from Ossitalia, the company which worked on the installation of the medical gas equipment, have been charged in connection with the deaths.
Tonganoxie family reaches settlement in medical gas accidentcase(20) [January 28, 2011]
The family of a 20-year-old Tonganoxie High School graduate who suffered brain damage during a 2009 dental procedure in Lawrence reached a $3 million settlement Thursday with a Lawrence plumbing company.But legal action is pending against several defendants, including the city of Lawrence, in the case that was filed on behalf of Austin Stone. A trial is scheduled for November.The lawsuit, which was filed on behalf of Stone and his guardians, Tara Passmore and Lance Stone, alleges that oxygen and nitrous oxide lines were crossed during design and construction of Dr. Kirk Vincent’s office at 4811 Bob Billings Parkway.
Call for action after girl dies(18):
NajiyahHussien died after mix up
The father of a three-year-old girl who was fatally starved of oxygen in a hospital mix up has called for action to prevent a similar tragedy.NajiyahHussain was taken to Newham General Hospital after suffering a fit at her home in East London.She died after being given nitrous oxide instead of oxygen.Nitrous oxide, or laughing gas, is used as an anesthetic.
Medical Gas Mix Ups in India-[6/7/2011](21)
MADURAI: The Madurai Bench of the Madras High Court has sought the government as well as private hospitals to submit a list of best neurologists to help treat the woman from Nagercoil who slipped into coma after nitrous oxide was wrongly administered during a family planning surgery.Rukmani (37), wife of Ganesan from Nagercoil, was admitted to the Nagercoil Government Hospital for the surgery.During the treatment, she was administered nitrous oxide instead of oxygen after which Rukmani went into coma.She was taken to Government Rajaji Hospital in Madurai for further treatment.
Under these circumstances, Ganesan filed a writ petition at Madurai Bench seeking action gainst the person involved in wrong treatment and also to provide compensation to his family.When the writ petition came up for hearing before Justice R Sudhakar, the government pleader said that Kanyakumari District Collector has already provided a compensation of Rs 50,000 to the family and from Madurai District administration boarding facilities were being provided to Ganesan and his family in GRH itself, he pointed out.
Ganesan told the court that there is improvement in the condition of Rukmani due to the good treatment given by the doctors.Upon hearing this, the judge ordered a list of best neurologists be submitted to the court by Tuesday so that further treatment can be provided to Rukmani.