Preparation. Manufacture. Pharmacology of Nitrous Oxide. History of Nitrous Oxide - N 2 O

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Leslie Rich
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Pharmacology of Nitrous Oxide Aim The effects of inhalation sedation (N2O)on the body and its hazards Learning objectives By the end the students should know:- The properties & characteristics of N2O

work History of Nitrous Oxide - N 2 O 1771 Joseph Priestley discovered OXYGEN. 1772 Joseph Priestley discovered NITROUS OXIDE.

1 Pharmacology of Nitrous Oxide Aim The effects of inhalation sedation (N2O)on the body and its hazards Learning objectives By the end the students should know:- The properties & characteristics of N2O How is it absorbed/eliminated by body Effects of N2O on Organs systems The adverse effects/complications of N2O Health and safety issues around N2O About scavenging the reason for/types & how they work History of Nitrous Oxide - N 2 O 1771 Joseph Priestley discovered OXYGEN Joseph Priestley discovered NITROUS OXIDE Humphrey Davey discovers some of the effects of Nitrous Oxide 1840s Horace Wells, a dentist, employed Nitrous Oxide as anaesthetic 1888 Liverpool Dental Hospital used Nitrous Oxide analgesia for cavity preparation on teeth Dr Harry Langa in the USA began using Nitrous Oxide analgesia. He was later to write the standard textbook on Relative Analgesia. RA is inhalation sedation using a mixture of N2O & O2 The patient is awake, but has a reduced level of fear and anxiety Manufacture Ammonium Nitrate crystals is heated between 250 and 270 o C, NH 4 NO 3 N 2 O + 2H 2 O purified, and stored in compressed form in metal cylinders Preparation 30% N2O in liquid form in full cylinder The pressure gauge (800psi) measures the vapor pressure of the liquid Weighing the cylinder is the only way of knowing how much gas is left!!!!!!! N20 e size cylinder weighs 5.4kg empty, 3.37 gas = 8.97kg when full 1

2 Physical properties of N20 Physical Properties Its one and a half times heavier than air (specific gravity 1.53) Only inorganic substance other than CO2 to have CNS depressant properties Only inorganic gas used to produce anesthesia in humans N 2 O constitutes % of the earth s atmosphere!! Physical Properties N2O require heat for vaporization into gaseous state Relatively insoluble in blood : blood-gas solubility coefficient is 0.47 at 37 C Nitrous oxide is carried in simple solution in the body and does not enter into any chemical combination during administration SOLUBILITY The Solubility in blood of an agent is expressed as the BLOOD GAS DISTRIBUTION COEFFICIENT The Blood Gas Distribution Coefficient is the ratio of the number of molecules of the agent in the blood phase, to the number of molecules in the gaseous phase, per unit volume, at equilibrium. SOLUBILITY The solubility of Nitrous Oxide in the blood is an important consideration because it effect the rate of absorption, distribution and rate of excretion. The inhalation agent N2O is administrated as a gas Inhalation Absorption BGDC for N2O is 0.47 compared to Halothane which has BGDC of 2.36 and Diethyl Ether Nitrous Oxide is poorly soluble in blood therefore induction and recovery are rapid. The Lungs 2

MOVEMENT OF NITROUS OXIDE DOWN PARTIAL PRESSURE GRADIENT N2o is rapidly absorbed into the CV due to large concentration gradient of N2O between alveolar sacs and blood N20 reach the brain by crossing

displacement of N2 by N2O, usually in 3-5 minutes Tissues with greater blood flow (brain, heart, liver, kidney) receive greater amounts of N2O Absorption Tissues with poor blood supply (fat, muscle,

3 MOVEMENT OF NITROUS OXIDE DOWN PARTIAL PRESSURE GRADIENT N2o is rapidly absorbed into the CV due to large concentration gradient of N2O between alveolar sacs and blood N20 reach the brain by crossing alveolar membranes into the blood Nitrous oxide is carried in simple solution in the body and does not enter into any chemical combination during administration Absorption CNS saturation occurs by displacement of N2 by N2O, usually in 3-5 minutes Tissues with greater blood flow (brain, heart, liver, kidney) receive greater amounts of N2O Absorption Tissues with poor blood supply (fat, muscle, connective tissue) absorb small amounts Alveolar and grey-matter tension during uptake of 25% nitrous oxide Proportional saturation for 25% N 2 O 1.0 Slow absorption occurs once primary saturation has completed There is no body reservoir present once N2O terminated Alveolar tension Grey-matter tension Time in minutes ELIMINATION OF NITROUS OXIDE Elimination of N2O Returning with the blood to the left side of the of the heart and are then distributed through the arterial supply to lung. ELIMINATION Hence movement of N2O down partial pressure gradient 3

4 Biotransformation N2O undergoes no biotransformation in the body Majority of N2O is exhaled unchanged 3-5mins following termination of delivery 1% eliminated via skin and lungs in 24hrs DIFFUSION HYPOXIA Rapid diffusion of large volumes of N 2 O into the alveoli produces a significant dilution of O 2 present. In normal alveolus air contains at least 16 % O 2. For few minutes on termination of RA the O 2 may drop to 10%!! There is a rapid diffusion of N 2 O from the blood into the alveoli. This decreases CO2 arterial tension with decrease stimulus for respiration and this also dilutes the O 2 present, causes the hypoxia. Hypoxia causes headache, nausea, and lethargy-hangover effect. however Prevent DIFFUSION HYPOXIA by giving 100%oxygen for 2-3 minutes. Potency Nitrous oxide is the least potent of all anaesthetic gases Potency is expressed in terms of a Minimal Alveolar Concentration for an agent (MAC) MAC The concentration of the inhalation anaesthetic required to abolish the response to a standard surgical stimulus in 50% of the patients Minimal Alveolar Concentration of N2O is high about 104% POTENCY As N2O has a high MAC hence a low potency probably the lowest potency value of all the anaesthetic gases therefore very safe. Potency of N2O N2O in sub-anaesthetic dosages can produce analgesia N20 + O2 at 20%/80% mix = to 10-15mg of morphine Optimal concentration is 35% 4

Nitrous Oxide has the following properties and characteristics:- Anxiolytic properties hence it will reduce the distressing feeling of tension, anxiety, so inducing a state of relaxation and panic

5 Nitrous Oxide has the following properties and characteristics:- Anxiolytic properties hence it will reduce the distressing feeling of tension, anxiety, so inducing a state of relaxation and panic Analgesic It is estimated that a 20% : 80% mixture of N 2 O - O 2 produces the analgesic effectiveness of 10-15mg of morphine. So what are:- The Effects of Nitrous Oxide on organ systems Amnesia Preventing recall of events that occurred after the sedation was given Weak anesthetic agent Actions of Nitrous Oxide on CNS Nobody really knows the action of N 2 O on the CNS Latest theory is that it affects the NMDA glutamate receptors N-methyl-D-aspartate excite the nerves N2O blocks their ability to detect a normal signal - sedating Cardiovascular system No changes in heart rate or cardiac output BP remains stable with only slight decrease Cutaneous vasodilatation Respiratory System N2O is non-irritating to pulmonary epithelium Changes drop in respiratory rate and depth more likely due to anxiolytic effects Slight elevation of resting respiratory minute volume at 50%/50% mix GI System No clinically significant effects unless there is an obstruction N/V rarely seen unless hypoxia present Can be used in hepatic dysfunction 5

Hematopoietic System Long-term exposure greater than 24hrs can produce transient bone marrow

helps relaxation Reproductive System Uterine contraction not inhibited Pregnancy is a relative

Acute Complications Excessive perspiration peripheral vasodilatation 2-3% incidence If pallor,

6 Hematopoietic System Long-term exposure greater than 24hrs can produce transient bone marrow depression Musculoskeletal System No direct relaxation of skeletal muscle Anxiolytic effects helps relaxation Reproductive System Uterine contraction not inhibited Pregnancy is a relative contra-indication (avoid 1 st trimester) Complications and Adverse Reaction of Nitrous Oxide Acute Complications Excessive perspiration peripheral vasodilatation 2-3% incidence If pallor, decreased blood pressure, increased heart rate- consider syncope (100% O2 ) Treatment - decrease N20% 6

7 Acute Complications Nausea Causes over sedation - especially >50% long procedures anxious patients inherent tendency full stomach?? Treatment decrease N2O Complications Vomiting Potentially serious aspiration pneumonia, obstruction Pediatric more often than adult Early recognition of nausea is key to prevention Vomiting Signs pallor Complications sweating cold / clammy increased salivation active swallowing Complications Vomiting Management 100% O2 remove dental instrumentation & rubber dam turn head to side emesis basin - high volume suction replace nasal hood - 100% mins Complications Shivering Rare Usually at end of procedure Treatment Reassurance, blanket Sexual Phenomena Sexual hallucination/arousal Females more frequent Precautions Always have assistant present Avoid concentrations >50% Never leave patient unattended 7

8 From a Health and Safety prospective:- Is there a problem With N2O pollution??? Animal studies have demonstrated adverse effects at exposure to high levels so the potential for harm cannot be dismissed BDA Advise sheet A3 - March

9 Retrospective study of 459 dental nurses in California into the association between N 2 O occupational exposure and fertility. Significant reductions only in those exposed to unscavenged N 2 O for more than 5 hours per week. Rowland et al, 1992 Adverse reproductive outcomes are linked to B12 deficient individual and those exposed to high nitrous oxide levels Workforce Exposure Levels (WEL) / Occupational Exposure Standards (OSEs) are based on an 8 hour time weighted average (TWA) In the UK the WEL /OSE for 9

8ppm Scavenging Not Scavenged but vented into the local environment Leakage from

10 Understanding Time Weighted Average (TWA) 8 hour TWA therefore equals 250 X 3/8 = 93.4ppm But if operator works 2 sessions per day TWA = 186.8ppm Scavenging Not Scavenged but vented into the local environment Leakage from breathing delivery system ie mask Leakage from circuit Exhaled breath What is it? Why use it? What are the benefits? 10

MediScav Active Scavenger Unit Description: Comes complete

sound proofed Carrying handle The pump requires an exit vent

11 MediScav Active Scavenger Unit Description: Comes complete with external debris filter/ outlet, one metre 30mm transfer hose and vent warning label. Unit is CE marked, requires a 240v power point and external wall vent Price: Description: The New Miniscav active scavenger unit Fully sound proofed Carrying handle The pump requires an exit vent through an external wall for: waste hose assembly ( 25) Additional 20mm transfer hose 10/m Certosimo et al 2002 N2O Scavenging - Device 11

Active Scavenging achieves < 100ppm 71%-91% >50ppm ACTIVE + PASSIVE needed to achieve US standard of 25 ppm TWA Certosimo et al 2002 check (at least once a week) that scavenging and

Periodically review how you operate scavenging equipment to ensure that it is being used correctly.

Sheet Summary Induction Characteristics Smooth Properties of How does an ideal sedative Anxiolysis Yes Cardiovascular stability Stable Ease of titration Easy Induction and recovery Rapid

12 Active Scavenging achieves < 100ppm 71%-91% >50ppm ACTIVE + PASSIVE needed to achieve US standard of 25 ppm TWA Certosimo et al 2002 check (at least once a week) that scavenging and ventilation equipment are working properly and have it regularly serviced in accordance with the manufacturer s recommendations and at least every 12 months. Periodically review how you operate scavenging equipment to ensure that it is being used correctly. Make sure your employees are aware of the possible risks to their health, understand why scavenging and ventilation are necessary and how to use the equipment properly BDA A3 Advise Sheet Summary Induction Characteristics Smooth Properties of How does an ideal sedative Anxiolysis Yes Cardiovascular stability Stable Ease of titration Easy Induction and recovery Rapid Metabolism O% Ease of breathing Non-pungent Blood Gas Solubility Low Potency (MAC) Weak Speed of change in sedation level Rapid Systemic toxicity potentially None Environmental effects None Analgesia Yes N2O rate? Yes Yes Stable Easy Rapid 1% Non-pungent Low Weak Rapid Yes prolonged use Yes Yes ANY QUESTIONS? 12

Figure 5. Nasal mask in place

Figure 5. Nasal mask in place Clinical procedure Having checked that the inhalational sedation machine is working and that extra gas cylinders are available (or that piped gases are flowing), and that the breathing system is assembled