Waiting to Inhale

Journal Reviewed:  Anaesthesia
Issues: April 1999 and September 1999
Abstracted by: Dr J Groves  MB BCh (Registrar, University of the Witwatersrand)

Summary of abstracts

A feast of respiratory related articles

You may also wish to briefly browse our editorial comment

1.  Ventilatory patterns & associated episodic hypoxaemia in the late postoperative period in the general surgical ward

Postoperative episodic oxygen desaturation occurs early and late. It can precipitate myocardial ischaemia and cardiac arrhythmias. The aim of this study was to systematically describe ventilatory patterns and associated hypoxaemia on the 2 nd and 3 rd postoperative nights following major abdominal surgery. The pathogenesis of late episodic desaturation has been related to postoperative sleep disturbances but may also be due to hypopnoeas and apnoeas.

The Edentrace II was used to measure impedance pneumography, pulse oximetry, heart rate and oral-nasal airflow. 30 patients where recruited on the afternoon of day 2 postop. 2 of which were excluded because of equipment malfunction and 10 of the remaining 28 refused monitoring on the 3 rd night. In total 46 study nights were examined. The patients were classified as heavy, light or non-snorers, using the Epworth sleepiness scale questionnaire. Measurements were taken between 23h00 – 07h00 on nights 2 and 3.

Results showed that ventilatory disturbances were common and included periods of hypopnoea and obstructive, central and mixed apnoeas. Overall, the median respiratory disturbance index (apnoeas + hypopnoeas per hour) was 12 and the patients spent 6% of the night in some kind of ventilatory disturbance. Interestingly there was no significant difference between patients receiving IM morphine and epidural analgesia; smokers and non-smokers; and snorers and non-snorers. There was statistically significant correlation between age and total number of apnoeas per hour and number of mixed and obstructive apnoeas. Surprisingly, weight correlated to the duration of central apnoea only.

A median of 23% of hypopnoeas and 7% of apnoeas were linked to episodes with oxygen desaturation. According to the authors the physiological explanation is unclear but the results were possibly due to the definitions used (Apnoea = no air flow for more than 10 seconds, hypopnoea = decreased air flow of 50% below average amplitude for at least 10 seconds with 3% decrease in oxygen saturation and episodic oxygen desaturation = decrease in oxygen saturation of >5% below baseline for more than 10 seconds).

The inability to predict postoperative oxygen desaturation from preoperative snoring habits may be related to the size of the study sample.

The main finding was a high incidence of ventilatory abnormalities on the 2 nd & 3 rd postoperative nights and that a high proportion were associated with desaturation events. Early episodic desaturations (within the first 8 hours postoperatively) are associated with disturbances of ventilation e.g. obstructive apnoea, paradoxical breathing and periods of slow respiratory rate, often due to the residual effects of general anaesthetics and opioid analgesia (Catley et al). However, late episodic desaturation on the 2 nd & 3 rd postoperative nights, may be related to anaesthetic, surgical and pharmacological effects on breathing patterns. The main reason for ventilatory abnormalities is sleep disturbance with rebound of REM sleep. The authors suggest that this could be minimised by decreasing surgical stress response and the use of opioids for postoperative pain relief.

Article 1: Ventilatory patterns & associated episodic hypoxaemia in the late postoperative period in the general surgical ward
Journal:  Anaesthesia, April 1999, Vol. 54, p 323-328
Article type:  Clinical Study
Authors:  Rosenberg, J.  Rasmussen, G.   Reinhold Wøjdemann.  et al.

2.  The cardiorespiratory effects of laparoscopic procedures in infants

Paediatric surgeons have been using laparoscopic techniques since the 1970’s. Despite the benefits of laparoscopy, insufflation of CO 2 causes intra-operative ventilatory and haemodynamic changes. Data on the effects on infants is limited. The aim was to investigate respiratory changes, to ascertain the complications of pneumoperitoneum in infants, and to clarify the safety of the procedure from an anaesthetist’s perspective.

This is a poorly designed and implemented study. 36 infants with various diagnoses, undergoing elective laparoscopic procedures were recruited – inclusion & exclusion criteria were not stated. Procedures ranged from explorations and biopsies to Kasais. Durations ranged from 30-400min. Only 27 were studied. The authors state that the patients were monitored and anaesthetised in standardised manner. The suspicious methods used included gas induction with halothane or isoflurane, manual ventilation with Jackson–Rees's modification of Ayers' T piece at a rate of 20bpm for all, capnography used in only 8 cases and arterial cannulation for every patient.

Serial arterial blood gases were taken. Respiratory parameters measured showed a decrease in pH, PaO 2 , SaO 2 & SpO 2 and an increase in PaCO 2 following CO 2 insufflation. Not surprisingly these improved after desufflation. Changes in pH and PaO 2 were statistically significant. Haemodynamic changes (heart rate & systolic blood pressure) were not statistically significant.

Infants have a lower FRC and higher closing volumes compared to adults. These differences are aggravated by patient position, pneumoperitoneum and general anaesthesia in laparoscopic surgery. It is important to remember that end tidal CO2 may be unreliable when respiratory rate is rapid, tidal volumes are low and with the Jackson-Rees breathing system.

Article 2: The cardiorespiratory effects of laparoscopic procedures in infants
Journal:  Anaesthesia, Sep 1999, Vol. 54, p 831-834
Article type: Clinical Study
Authors: Bozkurt, P.  Kaya, G.  Yeker, Y.   et al.

3.  Time course of changes in breathing pattern in morphine and oxycodone induced respiratory depression.

The aim of this study was to describe the time, dose and concentration dependence of changes in breathing patterns in opioid-induced respiratory depression for IV morphine & oxycodone.

6 healthy males volunteers took part in this random, double-blind and cross-over study which consisted of giving equipotent dose of an opioid via an IV bolus followed by a 2 hour infusion, in two separate study sessions. Respiratory-inductive plethysmography continuously measured breathing patterns. Haemodynamics were monitored invasively along with pulse oximetry and serial arterial blood gases. Gas chromatography measured oxycodone levels and high performance liquid chromatography was used for morphine levels.

The results showed a similar time course of changes in breathing pattern for both drugs

  • Initial decrease in respiratory rate (and minute ventilation) with an increase in the rib cage contribution to tidal volume.
  • An increase in PaCO 2 due to a decreased minute ventilation
  • Compensatory increase in tidal volume to try and increase minute ventilation.
  • A decrease in the inspiratory duty (inspiratory time/total cycle time).  This was suprising as it was thought to only occur in intrinsic lung pathology.

There was noted to be more profound respiratory depression in the oxycodone group, as four of the infusions had to be terminated early (99 ± 14min).  They dose relation 1mg oxycodone = 0.78mg morphine was used as assessed in the intravenous treatment of cancer pain, a relationship that may well be inaccurate in their healthy male population.

A respiratory rate of less than 8 breaths per minute is an inadequate clinical guide to opioid induced respiratory depression.  A better specificity can be acheived by including non invasive respiratory inductive plethysmography to detect the increase in the rib cage contribution to the tidal volume.

Article 3: Time course of changes in breathing pattern in morphine and oxycodone induced respiratory depression.
Journal: Anaesthesia, Sept 1999, Vol. 54, p835-840
Article type: Labaratory study
Authors: Leino, K.  Mildh, L.  Lertola, K.   Seppälä, T.  Kirvelä, O.

4.  Sevoflurane: a comparison between vital capacity and tidal breathing techniques for the induction of anaesthesia and laryngeal mask airway placement.

There appears to be no clinical significant difference between gas induction with sevoflurane using the vital capacity or tidal breathing technique. So a prospective randomised trial was carried out.

In an extremely well designed study, 60 adult day-case patients were randomly assigned to either vital capacity or tidal breathing inhalational induction. The end points used were time taken: for loss of eyelid reflex, to drop a weighted syringe, to jaw relaxation and to end of laryngeal airway insertion.  An interesting clinical point is that intravenous access was only secured after the laryngeal mask was in place.

Definitions –

Vital capacity technique . The patient was instructed to breath in as deeply as possible and then to breath out to residual volume. The next deep breath was then taken from the facemask connected to a Bain circuit with a 4L reservoir bag that had been primed for 45seconds with 30% oxygen, 70% nitrous oxide and 8% sevoflurane. The patient was asked to hold this breath for as long as possible.

Tidal breathing technique . The patient was instructed to breath as normally as possible from the face mask connected to a Bain circuit with a 4L reservoir bag, the fresh gas flow was 30% oxygen, 70% nitrous oxide and 8% sevoflurane.

The results showed no statistical or clinical significant difference between the two techniques, including

  1. Time from first breath of fresh gas flow to insertion of laryngeal mask airway
  2. Complications of induction
  3. Complications of laryngeal mask insertion
  4. Cost of fresh gas flow from first breath to the end of laryngeal mask insertion.

The authors pointed out two types of possible bias

    1. Selection bias – study selected for needle phobic patients who are more likely to tolerate a gas induction.
    2. Observer bias – the investigator was not blinded to the technique used.

Their conclusion is that the vital capacity method is technically more demanding, requires a motivated patient and a degree of training prior to induction. Poor patient technique, difficulty in the supine position and loss of good seal around face mask lead to submaximal volatile being available. The cost of priming the circuit for 45 seconds with the fresh gas flow prior to the patient taking the first breath made the vital capacity technique more expensive.

Article 4: Sevoflurane: a comparison between vital capacity and tidal breathing techniques for the induction of anaesthesia and laryngeal mask airway placement.
Journal:  Anaesthesia, Sept 1999, Vol. 54, p841-844
Article type:  Clinical study
Authors: Baker, C.  Smith, I.

5.  Xenon: recent developments

Xenon is Greek for stranger. It was discover in 1898 and found to be the only noble gas to be anaesthetic under normobaric conditions. Xenon is extremely scarce with an average room containing only 4ml.

Manufacture is by fractional distillation of air and costs 2000 times more than N 2 O.

Commercial uses include lasers, high intensity lamps, flash bulbs, aerospace, X-ray tubes and in medicine.

Physical properties

  • Colourless, odourless, tasteless.
  • Monatomic gas, atomic number = 54, molecular weight = 131,3
  • 9 stable isotopes.
  • Freezing point -111,9 o C, Boiling point -107,1 o C.
  • 4 times more dense than air.
  • Nonflammable and will not support combustion.
  • Diffuses freely through rubber and silicone components.

Anaesthetic agent

  • Very close to the ‘ideal agent’.
  • First used in 1951 by Cullen on an 81yr old man having an orchidectomy.
  • No occupational/ environmental disadvantages.
  • MAC = 71%. (With more widespread usage the Russians have noticed the MAC to be closer to 60%)
  • Minimal haemodynamic effects.
  • Lowest blood/gas partition coefficient = 0,14 of currently available inhalational agents.
  • Low oil/water partition co-efficient of 20. 
  • Rapid induction and eduction regardless of duration of administration
  • 4 stages of anaesthesia noted with 70% Xenon/ 30% oxygen.
      1. Whole body paraesthesia & hypo-algesia.
      2. Euphoria & increased psychomotor activity.
      3. Analgesia with partial amnesia (after 3-4min).
      4. Surgical anaesthesia with a degree of muscle relaxation.
  • Equivalent analgesia when compared with equipotent doses of N 2 O  The analgesia produced by both gases is not reversible by naloxone.

Specific effects on the body

  • Respiratory
    • Central depression causes a decrease in respiratory rate with a compensatory increase in tidal volume and can progress to apnoea
    • Higher density and viscosity (compared with oxygen, air and  N 2 O) theoretically makes xenon more likely to increase airway resistance. Clinically the airway resistance is slightly less than that seen with N 2 O and it can be used safely in lung disease
    • Diffusion hypoxia is very mild as the blood/gas partition of Nitrogen (0.014) is only 10 times less than that of Xenon (0.14) as opposed to the almost 40 times less than Nitrous Oxide (0.47)
  • Cardiovascular
    • No significant change in contractility, blood pressure and systemic resistance.
    • Some reports of decrease in heart rate with variability in rhythm.
    • May attenuate the  myocardial depressant effects of isoflurane.
    • No inhibitory effects on cardiac ion channels i.e. calcium, sodium and inward potassium channels.
    • In an animal study, xenon anaesthesia produced the highest regional blood flow to brain, liver, kidneys and GIT.  The control groups were 1% halothane in Nitrous oxide and thiopentone with fentanyl.
  • Central nervous system
    • Xenon 133 can be used to measure cerebral blood flow. There are reports questioning the accuracy as the agent appears to increase cerebral blood flow. This increase in cerebral blood flow is reveresed by mild hyperventilation
    • Xenon increases cerebral blood flow, increases intracranial pressure and decreases cerebral perfusion pressure in acute head injury patients.  This is not associated with cerebral oligaemia or ischaemia.
    • At present it is not recommended for neurosurgery.
  • Renal
    • No data available.
  • Endocrine/neurohumoral
    • Attenuates surgical stress due to analgesia.  Does not have any short or long term cortisol suppresion effects.
  • Toxicity
    • Platelet aggregation potentiated at 2atm (relevant to deep-sea divers).
    • No reported haematological toxicity.
  • Malignant hyperthermia
    • Seems not to trigger malignant hyperthermia.
  • Metabolism and elimination
    • Unlikely to be involved in any biochemical events in the body.
    • Eliminated via the lungs.
      • Under special conditions xenon is capable of forming compounds with very reactive elements e.g. clathrates, fluorides & chlorides

Potential ways to make xenon anaesthesia economically acceptable.

  • Decreasing manufacturing costs.
    • This is only practical in large air separation plants.
    • Current price is 10 US$/ litre
    • Manufacture will increase as aerospace applications grow, but as this xenon is then lost to the atmosphere this will not contribute to decreasing the cost.
  • Use in a fully closed breathing system
    • Use of semiclosed systems (facemasks/LMA/spontaneous breathing) cost £1200/hr.
    • Very low flow e.g. 0,3 l/min will cost £160-180/hr.
    • Fully closed automated systems are available that are suitable for xenon anaesthesia
      • Gas piston circle
      • physioflex device
      • Balanced circle systems.
      • Circle priming
  • Recycling devices.

Gas analysis

Xenon can be measured with mass spectrometry, piezoelectric absorption, thermal conductivity and ultra-sound.


  • Colourless and odourless gas with no irritation to the respiratory tract.  Well tolerated with gas induction
  • Low blood/gas and oil/water partition co-efficients allowing rapid induction and eduction
  • Produces unconsciousness with analgesia and a degree of muscle relaxation
  • MAC of 60-70% allows a reasonable inspired oxygen concentration
  • It does cause respiratory depression, to the point of apnoea.
  • It is cardiac stable.
  • Not metabolised in the body and is eliminated rapidly and completely via the lungs.
  • It is non toxic and is not associated with allergic reactions
  • Stable in storage, no interaction with anaesthesia circuits or soda lime.  Should not be used with rubber anaesthesia circuits as there is a high loss through the rubber
  • Non flammable
  • Expensive

Owing to environmental concerns there may be no alternative but to use xenon even if it incurs an increase in cost.

Article 5: Xenon: recent developments
Journal:  Anaesthesia, April 1999, Vol. 54, p 335-346
Article type:  Review Article
Authors: Dingley, J. Ivanova-Stoilova, T.  Grundler, S. Wall, T.


Editorial pointers

In article one, Rosenberg et al claim to have shown a high incidence of ventilatory abnormalities on the second and third post operative nights, and that a high proportion of these were associated with  desaturation.  There are several problems with this study.
  • Rather than looking at each patient's actual ventilatory parameters and telling us how many of their patients actually had ventilatory disturbances, they used the pooled data of 46 study nights and tell us it corresponds to 15/28 of their patients having more than 5 apnoeas/hour on at least one study night.
  • When looking for a cause of ventilatory disturbances their study design was too poorly designed to show a difference, or the difference they showed was clinically irrelevant
    • Effect of monitoring.
      • 10 out of 28 people refused a second night of monitoring.  This is never explained but the suggestion is there that the monitoring itself disturbed them.
    • Analgesia. 
      • They said there was no difference between the epidural group and the intramuscular morphine group
      • Patient demographics showed that the epidural group was receiving morphine at a rate of 200 micrograms per hour!
    • Patient Characteristics
      • Snorers - No preoperative assessment was made of the snoring patterns, rather subjective hearsay was accepted!
      • Weight - a correlation of r=0.47 would only account for 22% of the central apnoeas.   Although just statistically significant this correlation does not explain the clinical findings
      • Age - correlation of r=0.16, accounting for 2.5% of the total number of apnoeas/hour.   This correlation to does not explain the clinical findings

Their conclusion that  "{we}should aim at minimising late postoperative ventilatory disturbances, probably by decreasing surgical stress response and the use of opioids for post operative pain relief" has no support from the article itself.   There was no mention of the possible role of routine oxygen supplementation.

The aim of article 2 was to asses the cardiorespiratory effects of laparoscopy.

In terms of the respiratory effects any PaCO 2 and PaO 2 measures they made are invalidated because:-

  • A single anaesthetist manually ventilated these children with a functional Mapelson D type breathing system. 
  • The authors state the fresh gas flow was 4L/min using this breathing system where the actual minute ventilation is entirely dependant on the fresh gas flow.  The demographics show that the weight varied from 2.7 to 13Kg. 

The cardiac status of the children was remarkably stable, perhaps because:-

  • There was no physiological affect from the PaCO 2 .  What is interesting is that despite the inaccuracies of a capnograph in the situation, the values of F ÉCO2 were good approximations in the cases in which it was used
  • The PaO 2 was kept at high levels by increasing the FiO 2 .  Good ventilation and the addition of PEEP must also be considered
  • They had excellent surgeons who kept the intra-abdominal pressures below 10mmHg
  • The fluid status of the patients was good.

A well designed and implemented study, which gives useful clinical insight into the respiratory changes of laparoscopic surgery in children is..

Changes in Respiratory Mechanics during abdominal laparoscopic surgery in children. 
Bergesio, R.  Habre, W.  Lanteri, C.  Sly, P. 
Anaesthesia and Intensive Care 1999; 27: 245-248

An excellent study design and implementation is found in article 4.
Medicine and anaesthesia are arts and not sciences.  There are often no "right" answers, but there will always be fanatical support available for each side of an issue.  This excellent study must put some doubt into the mind of even the most ardent supporter of vital capacity sevoflurane induction.


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