AMSORB® PLUS is NOT a Soda Lime

The world’s first strong-alkali free absorbent

Terminology Tidal Volume Minute Volume Rebreathing FiCO2 Is the amount of volume in one breath. Minute Volume Respiratory minute volume (or minute ventilation) is the volume of gas inhaled in one minute. Rebreathing When exhaled CO2 is re-inhaled. FiCO2 Fractional Concentration of Inspired CO2. The amount of CO2 inspired during inspiration.

Terminology High Flow anaesthesia Low Flow anaesthesia Flow higher than the patients minute volume. Low Flow anaesthesia less than the patients minute volume. Minimal Flow Anaesthesia Less the 1litre.

Why use a CO2 Absorbent? High Flow Anaesthesia 4-10L/min fresh gas flow AMSORB® PLUS

Why use a CO2 Absorbent? Low Flow Anaesthesia 0.25-4.0L/min fresh gas flow AMSORB® PLUS

Why use Low Flow Anaesthesia Environmental Benefits Using High Flow Rates entails using high volumes of anaesthetic vapour CO₂ and high levels of residual anaesthetic vapour may be scavenged and released into the environment Financial Calculation of using 2% Sevo with High and Low Flow Rates % Sevo Fresh Gas (L. min) Sevo Cost / hour Amsorb Plus Cost / hour 2% 4L $14.40 $0.94 2% 2L $7.20 $1.31 2% 0.5L $1.80 $2.65 Moderate Absorbent Cost Increase = 8-Fold Decrease in Vapour Cost 71% Reduction 48% Reduction

How Does a Soda Lime Absorb CO2 Sodium hydroxide serves to accelerate carbon dioxide absorption. Carbon dioxide and the water contained in the soda lime react to form carbonic acid: CO2 + H2O = H2CO3. Carbonic acid reacts exothermically with sodium hydroxide to form sodium carbonate and water: H2CO3 + 2 NaOH = Na2CO3 + 2 H2O + heat

Free from Sodium, Potassium, Lithium and Barium Hydroxide Amsorb Plus has no Sodium Hydroxide. That’s the main difference. While it looks like a soda lime, smells like a soda lime, possibly tastes like a soda lime its not a soda lime. This is very important.

Chemical Formulations & Performance Composition of Absorbents AMSORB® PLUS is not a soda lime since it does not contain sodium hydroxide (NaOH). None of the risks associated with soda limes apply to AMSORB® PLUS. Leading brands of soda lime all contain NaOH. The main points to be discussed. AMSORB® PLUS Brochure Page 06

The significance of NaOH within a C02 absorbent Alkalinity of Soda Lime As CO2 is absorbed, the moisture within the granula of the soda lime is released Chemical reaction is exothermic As the moisture content decreases, concentration of NaOH increases At 5% moisture, soda lime causticity causes agent degradation Desiccated soda limes are treated as hazardous waste Soda lime can be safe to use, but desiccated soda limes are unsafe and start to produce toxins The challenge is, how to tell when it becomes unsafe to use? 4.1% 3.5% 16% So you say “So what I’ve got Sodium Hydroxide in my soda lime. What does it matter?” So here we try and explain the significance of Sodium Hydroxide. On the graph typically soda lime when its fresh has about 3.5% Sodium Hydroxide and about 16% moisture. As CO2 is absorbed, the moisture that’s within the granule of the soda lime is released. This chemical reaction is exothermic. It heats up and it releases moisture. So we now know as we travel along this graph and the drier the soda lime becomes the more caustic the soda lime becomes. So the Sodium Hydroxide percentage increases. Now soda lime can be safe to use and then at some stage it becomes unsafe and starts to produce the toxins. The challenge is we don’t know when it goes from being safe to being unsafe. 5% Moisture 0% AMSORB® PLUS Brochure Page 10

AMSORB® PLUS contains 0% NaOH

There is moisture in the canister, therefore there is moisture in the Soda Lime? The primary reaction is between CO2 and calcium hydroxide (Ca(OH)2) and water. This forms calcium carbonate (CaCO3) (Chalk) and water. Exothermic heat and moisture are by-products of CO2 absorption.

Colour Change Colour change with AMSORB® PLUS is permanent Typically people will go on colour change as an indicator. Soda lime colour change is not a reliable indicator. Coloration in soda lime reverts to original state when not used for a few hours. Colour change in soda lime is based on alkalinity (pH), however (pH) level is unrelated to whether its safe or unsafe. To use soda lime safely, it is necessary to dispose of a % of useable product. AMSORB® PLUS colour change is based on moisture content and is permanent. But the problem is, this is the product from GE you can see that it changed colour but if they don’t dispose of it immediately within a period of time it will revert back to its original colour. So the doctor may say “OK I know when my soda lime becomes unsafe because it will change colour”. But the colour change is unreliable. The second point to note is the colour change is based upon a change in the ph of the soda lime. But the ph level is unrelated to whether its safe or unsafe. What is relevant is how dry the soda lime is. Is it 16% moisture or is it less than 5% moisture, there is no reliable way to know that. So because AMSORB® PLUS contains no Sodium Hydroxide then the only risk there is with using dry product is re-breathing CO2. The colour change with AMSORB® PLUS is permanent and the colour change with AMSORB® PLUS is based upon moisture content. Is it 16% moisture or is it less than 5% moisture, there is no reliable way to know! AMSORB® PLUS Brochure Page 04

Soda Lime and Colour Reversal Caustics from the core of the granule slowly migrate to the surface and neutralize the carbonic acid. In this case, the pH level increases, the color change is reversed and the granule returns to a white or off-white color. Soda Lime Granule

Concentration of Hydroxide ions compared to distilled water pH Sliding Scales Concentration of Hydroxide ions compared to distilled water (14+) Desiccated Soda Lime (13.5) Fresh Soda Lime (11.7) Fresh AMSORB ® PLUS

AMSORB® PLUS is NOT a Soda Lime

AMSORB® PLUS has a permanent colour change AMSORB® PLUS has permanent colour change.

Application / Clinical Realities When do you change When do you change? Change at ¼ colour change Change at ½ colour change Change at ¾ colour change

Scenario One – ¼ Colour Change A Safe Practise is an Expensive Practice APSF - Six steps to safely use soda lime. Turn off all gas flow when the machine is not in use. Change absorbent regularly, Monday morning for instance. Change absorbent whenever colour change indicates exhaustion. Change all absorbent, not just 1 canister in a 2 canister system. Change absorbent when uncertain of the state of hydration. If compact canisters are used, consider changing them more often. Most hospitals are changing it when they see any colour change. If these steps are followed the volume of absorbent used will increase significantly Most hospitals are changing it when they see any colour change. And that’s because they know in the back of their minds somewhere that something goes wrong with a soda lime when it changes colour and so they don’t want to take any risks. If you are changing here our main strategy is going to be selling on using less absorbent. We know that if you are changing it this point, often the soda lime never becomes dry enough to cause and produce the toxins. ¼ Colour Change

Cost of safely using a soda lime A Safe Practise is an Expensive Practice Analysis of Discarded Soda Lime; Economic & Practice Implications Franklin V. Cobos II, M.D., Max T. Baker, Ph.D., John H. Tinker, M.D Department of Anesthesiology, Nebraska Medical Center, Omaha, Nebraska Usable absorption capacity remaining ranged from 14% to 73%, with an average of 45%. A safe practice is an expensive practice. Our challenge is to get hospitals away from comparing unit price. AMSORB® PLUS will be more expensive, but you could be using 3 times the amount of soda Lime. This publication showed that when a hospital uses that level of safe practice and disposes of it this early they could be throwing out up to 73% fresh absorbent. So the safe practice is actually an expensive practice. ¼ Colour Change

Scenario 2 – ½ Colour Change If changing on ½ colour change, indicates that there is some level of concern about: Colour reversal Production of harmful toxins Wasting usable product. If changing on ½ colour change, indicates that there is some level of concern about colour reversal and some level of the production of harm toxins. Clinicians maybe unfamiliar about this. If you allow it to go to half way there is a greater risk of colour reversal . A greater risk of the toxins being produced but they are still wasting some amount of fresh product. ½ Colour Change

Scenario Three – ¾ Colour Change (Breakthrough) Significant danger of exposing patients to harmful toxins. Carbon Monoxide Production The brand which produces CO at the lowest level is LoFloSorb – 525ppm. The brand which produces CO at the highest level is Medisorb – 13,317ppm! Carbon monoxide (CO) is not measured or monitored during anaesthesia. If you are changing at ¼ or ½ colour change, you will not experience what we are going to talk about now because soda lime is being used safely. But its costing money to use safely. If you use soda lime right thru to breakthru there is a significant danger of exposing patients to harmful toxins. Publications are worst case sencario – dont want to scare monger, but this is the level of carbon monoxide being produced. In the past we have discussed with doctors, Compound A. Compound A started the focus on soda lime. Compound A with sevolflurane was proven to be nefrotoxin in rats but never proven to be significant in humans. So we very rarely talk about Compound A anymore. What we do talk about is carbon monoxide. When carbon monoxide is mentioned, very often people think we have said carbon dioxide because they don’t want to think that they are producing carbon monoxide. This graph shows the different publications illustrating the different products and the amount of carbon monoxide that was produced. And this is worse case scenario so this doesn’t always happen with a soda lime but we consider that theres no reliable way of knowing when a soda lime becomes unsafe then this is a real risk. AMSORB® PLUS Brochure Page 08

Headache and Nausea Brain Damage - Death Unconsciousness Now 500 parts per million according to our friends from Massimo tells us that if you are exposed to 500 parts per million after 30 minutes you would have a headache and nausea. After 60 minutes you would be unconscious. After 90 minutes severely brain damaged or dead. So that’s 500 hundred parts per million.

AMSORB® PLUS is NOT a Soda Lime

The significance of NaOH within a C02 absorbent Production of Carbon Monoxide Consider: Could cases of post operative vomiting and nausea be attributed to the production of carbon monoxide by a soda lime? Is there the potential for this? If you have the opportunity to remove this potential, and it doesn’t cost you any more, in fact its costs less. Is trailing AMSORB something that should be considered? Fully Exposed! Consider, could cases of post operative vomiting and nausea be attributed to the production of carbon monoxide in soda lime. Is there potential for the this. If you have the opportunity to remove this possibility, and it does cost you any more, in fact its costs less. Is trailing AMSORB something that should be considered. Alkalinity of Soda Lime

The significance of NaOH within a C02 absorbent Production of Carbon Monoxide AMSORB® PLUS is the only product that does not produces CO All soda lime products are capable of producing CO when desiccated Colour change is not a reliable indicator to illustrate if you have entered the red zone or not When does CO start being produced? < 4.8% moisture, the causticity is such that it is sufficiently able enough to produce CO CO can be delivered in a bolus dose Carbon monoxide (CO) is not measured or monitored during anaesthesia. 4.1% 3.5% 16% So you say “So what I’ve got Sodium Hydroxide in my soda lime. What does it matter?” So here we try and explain the significance of Sodium Hydroxide. On the graph typically soda lime when its fresh has about 3.5% Sodium Hydroxide and about 16% moisture. As CO2 is absorbed, the moisture that’s within the granule of the soda lime is released. This chemical reaction is exothermic. It heats up and it releases moisture. So we now know as we travel along this graph and the drier the soda lime becomes the more caustic the soda lime becomes. So the Sodium Hydroxide percentage increases. Now soda lime can be safe to use and then at some stage it becomes unsafe and starts to produce the toxins. The challenge is we don’t know when it goes from being safe to being unsafe. 5% Moisture 0% AMSORB® PLUS Brochure Page 10

AMSORB® PLUS cannot produce CO

Formaldehyde (HCOH) AMSORB® PLUS is not a soda lime (NaOH) Leading brands of soda lime all contain NaOH NaOH causes anaesthetic agent degradation which has three side effects. Production of: Carbon Monoxide (CO) Compound A Formaldehyde (Only with Sevoflurane) HCOH is a potent inhalation irritant and carcinogen Postoperative nausea and vomiting (PONV) can be caused by HCOH inhalation Bedi A et al state “Sevoflurane is degraded to formaldehyde when passed through dry CO2 absorbents that contain strong alkali.” With only Sevoflurane. So here you can see Compound A. This is the chemical breakdown where Sevoflurane is degraded to Compound A. Not significant we believe in humans. However, further on in that chemical reaction Sevoflurane is broken down into something far more significant – formaldehyde. Formaldehyde is Sidex. Its used to decontaminate products and is very very toxic. HCOH is a potent inhalation irritant and carcinogen and should never be administered to patients. Postoperative nausea and vomiting (PONV) can be caused by HCOH inhalation. Point 1. None of the risks associated with soda limes apply to AMSORB® PLUS. Point 2. Self explanatory Point 3. Sodium hydroxide (NaOH) causes anaesthetic agent degradation which has three side effects; production of: Carbon Monoxide (CO) Compound A Formaldehyde Point 4. Formaldehyde (HCOH) is produced when passing sevoflurane through certain brands of desiccated absorbent. HCOH is a potent inhalation irritant and carcinogen and should never be administered to patients. Postoperative nausea and vomiting (PONV) is caused by HCOH inhalation. Point 5. Bedi A et al state “Sevoflurane is degraded to formaldehyde when passed through dry CO2 absorbents that contain strong alkali. Formaldehyde was not detected when sevoflurane was exposed to either fresh or dry Amsorb. AMSORB® PLUS

Chemical Formulations & Performance Composition of Absorbents AMSORB® PLUS is not a soda lime since it does not contain sodium hydroxide (NaOH). None of the risks associated with soda limes apply to AMSORB® PLUS. Leading brands of soda lime all contain NaOH. The main points to be discussed. AMSORB® PLUS Brochure Page 06

AMSORB® PLUS cannot produce HCOH

Absorption /Adsorption Definitions the process by which one substance, such as a solid or liquid, takes up another substance, such as a liquid or gas, through minute pores or spaces between its molecules. Adsorption the accumulation of molecules of a gas to form a thin film on the surface of a solid.

The significance of NaOH within a C02 absorbent Anaesthetic Drug Adsorption With soda lime there is an increased possibility of anaesthetic drug adsorption. 4.1% 3.5% 16% So you say “So what I’ve got Sodium Hydroxide in my soda lime. What does it matter?” So here we try and explain the significance of Sodium Hydroxide. On the graph typically soda lime when its fresh has about 3.5% Sodium Hydroxide and about 16% moisture. As CO2 is absorbed, the moisture that’s within the granule of the soda lime is released. This chemical reaction is exothermic. It heats up and it releases moisture. So we now know as we travel along this graph and the drier the soda lime becomes the more caustic the soda lime becomes. So the Sodium Hydroxide percentage increases. Now soda lime can be safe to use and then at some stage it becomes unsafe and starts to produce the toxins. The challenge is we don’t know when it goes from being safe to being unsafe. 5% Moisture 0% AMSORB® PLUS Brochure Page 10

Agent Adsorption Time Taken to Reach Drug Setting Soda lime becomes more caustic as it dries out A caustic soda lime has the ability to adsorb and break down the anaesthetic agent With soda lime there is an increased possibility of drug adsorption = Waste of anaesthetic drug Implications for the hospital = increased drug costs. So you mentioned a concern about the cost of Sevoflurane. This study shows the various different soda limes when they were dry, anaesthetic drug was passed though it and they measured how long it took to reach the setting of drug. So for example if you are using Sevoflurane you might set 4%. With Loflowsorb for more than 1 hour they were only delivering 10% of the drug that they set. Where does the drug go to? The drug is soaked into the soda lime. With soda lime there is an increased possibility of drug absorption. AMSORB® PLUS Brochure Page 09

Awareness of Adsorption of Anaesthetic Gases? Set to Deliver 4% Actual - Delivering 3.5% What we believe is happening is a doctor dials up his 4%. They dial up 4% the monitor maybe shows that its delivering only 3.8% and the doctor will blame 1 of 2 things. Either the gas analyser is wrong the vaporiser setting is wrong . Have you considered that it’s the soda lime. So what the doctor may do – he may dial 4.2 or 4.3% until he sees that he is delivering his 4% and he is happy. With this practice, drug usage will increase significantly. Dont compare price for price. Amsorb maybe more expensive however you may only need to change canister after 7-8 days, depending on practice, with soda lime is could be 3day. The key with AMSORB is to change by capnograpghy 0.5% FICO2 or 5mil mercury. For effective drug delivery With this practice, drug usage will increase significantly. Agent Adsorption

Overall spend was considerably less Safety with Savings Cost Implications Mannion et al, 2011 Cost implications of replacing soda lime with AMSORB® PLUS Soda lime changed as per APSF guidelines. AMSORB® PLUS was used until breakthrough. Change at 0.5%FiCO2 AMSORB® PLUS was 32% more expensive. 25% Reduction 58% Reduction Now wouldn’t it be great if we could prove this. If somebody could do a study. This was a publication produced at Euro Anaesthesia in 2011. Initially the doctor was not interested, didn't disagree with the findings – didn't believe they were significant enough to cause concern. Then during a day list, 3 patients took longer than normal to wake up. Something jogged memory and he changed soda lime Next patient was fine. Then agreed to undertake study to justify costs. Practice was to use soda lime safely and change AMSORB® PLUS at 0.5%FICO2 It cost him less because he used 50% less absorbent. But what he did not expect to see and which was even more interesting was that there was a 25% reduction in their anaesthetic drug and that was without them dropping flows. Overall costs, the bigger saving came from the drug. The effort to try and get doctors to lower flows can be very difficult, we thought we would justify the expense of AMSORB because you can safely lower your flows and that was very difficult to do. Now we can show that there would be savings with AMSORB without them lowering their flows whatsoever. Overall spend was considerably less 28% Reduction The key with AMSORB® PLUS is to change by capnometry (0.5% FiCO2 or 5mmHg). Don’t fear the colour change!

Take the AMSORB® PLUS Challenge Safety No risk to patient or end user Efficiency Excellent C02 Absorption Use less Anaesthetic Drug Lower gas flow Environmental Safe for Waste Disposal Non toxic Safe for land fill Change in technique, you don’t need to be concerned about changing AMSORB® PLUS until Breakthrough (FiCO2 of 0.5%). Our strategy is this, we have what we call the AMSORB challenge. So we are saying to the doctor look we have this information but we understand that you do believe us , try it for yourself. Go back and look at over the past 6 months what your average cost for anaesthetic gases is and soda lime and then use AMSORB for a month and compare the two. Please don’t compare on unit price, because if you do that you are not going to understand the full value AMSORB gives you. If there is any change in technique, it is we reassure the customer that with AMSORB you don’t need to be concerned about changing AMSORB until right thru until they see FICO2 of 0.5%. They go with that and that should be backed up by a min of 3/4 colour change, and if you can do that then you will use significantly less absorbent. The AMSORB® PLUS Challenge

Take the AMSORB® PLUS Challenge The Mannion study provides the basis for The AMSORB® PLUS Challenge The demonstrates that replacing soda lime with AMSORB® PLUS can achieve:  25.7% Annual Anaesthetic Gas Savings Annual savings of £168,404 per hospital with 50 operating rooms £4.91 savings per patient 58% less absorbent used As AMSORB® PLUS is inert it is disposed in domestic waste; the disposal of soda lime is 5 times more expensive per kilo than the disposal of AMSORB® PLUS. What can AMSORB® PLUS do for you? The AMSORB® PLUS Challenge

Take the AMSORB® PLUS Challenge Our strategy is this: Doctor, we have this information but we’re not asking you to simply believe us , we’re asking you to try it for yourself Don’t compare on unit price. Only looking at unit price doesn’t allow you to see and understand the full value of AMSORB® PLUS Look at your average monthly cost for anaesthetic gas and soda lime. Trial AMSORB® PLUS for a month and compare There is one vital change in technique. We must reassure the customer that with AMSORB® PLUS you don’t need to be concerned about changing on colour. AMSORB® PLUS needs to be used right thru until they see FICO2 of >0.5% They go with that and that should be backed up by about 3/4 colour change. If you can do that you will use significantly less absorbent. Our strategy is this, we have what we call the AMSORB challenge. So we are saying to the doctor look we have this information but we understand that you do believe us , try it for yourself. Go back and look at over the past 6 months what your average cost for anaesthetic gases is and soda lime and then use AMSORB for a month and compare the two. Please don’t compare on unit price, because if you do that you are not going to understand the full value AMSORB gives you. If there is any change in technique, it is we reassure the customer that with AMSORB you don’t need to be concerned about changing AMSORB until right thru until they see FICO2 of 0.5%. They go with that and that should be backed up by a min of 3/4 colour change, and if you can do that then you will use significantly less absorbent. The AMSORB® PLUS Challenge

The AMSORB® PLUS Approach Features AMSORB® PLUS contains no Sodium Hydroxide AMSORB® PLUS has a permanent colour change AMSORB® PLUS is the safest C02 absorbent available, it’s not capable of anaesthetic degradation 70+ independent clinical publications Benefits Colour change is a visual indicator Do NOT change until FiC02 exceeds 0.5%(5mmHg) Efficient drug delivery Less time to equilibration Safe handling & disposal Affordable cartridge options for all Anaesthesia workstations Saving – Compromise no Longer The AMSORB® PLUS Approach

AMSORB® PLUS Savings Road Map Savings will depend on practice. Most people will see low flow as less than 2 ltrs. Low flow is anything less that the patients tidal volume. The lower flow goes, the bigger the risk of using soda lime. If you lower your flow the % of co2 is higher, so therefore you make your soda lime work harder and it becomes drier quicker. With AMSORB, low flow can be used AMSORB® PLUS

Application / Clinical Realities When do you change When do you change? Change at ¼ colour change Change at ½ colour change Change at ¾ colour change

AMSORB® PLUS is NOT a Soda Lime

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