Eur J Anaesthesiol 2014; 31:447–449
EDITORIAL
Effects of anaesthesia on ventilation/perfusion matching Go¨ran Hedenstierna
European Journal of Anaesthesiology 2014, 31:447–449
Almost all general anaesthetics cause a loss of muscle tone. This does not preclude spontaneous respiratory efforts, but the static tone is reduced. The balance between inward forces (lung recoil) and outward forces (chest wall expansion) at the resting volume, namely functional residual capacity (FRC), is altered, with a decrease in the outward forces so that resting lung volume is reduced. The shift from upright to supine reduces FRC by approximately 0.7 to 0.8 l and general anaesthesia by a further 0.4 to 0.5 l.1 FRC is now close to residual volume - the volume reached by a maximum expiration. At this lung volume, airways in lower, dependent lung regions close during expiration. Some airways may open up during the next inspiration, however, with reduced ventilation in the subtended lung region and subsequent reduction in ventilation/perfusion ratios ˙ Other airways further down the bronchial tree, ˙ Q). (V= may stay closed during the whole breath and the subtended alveoli are not ventilated, causing shunt. The reason for the gravitational distribution of airway closure is the increasing pleural pressure down the pleural space, being negative in the upper region (apex in upright and anterior in supine position) and positive in dependent regions after a deep expiration.2 The oxygen in the gas trapped behind closed airways will rapidly be absorbed by the capillary blood flow and will not be replenished by gas from the outside via the trachea. Carbon dioxide is delivered to the alveoli from the blood, but diffuses easily into the lung tissue and the volume is normally smaller than the amount of oxygen absorbed. The alveoli shrink but are kept open by any remaining nitrogen. If ventilation is provided with 100% oxygen during the induction of anaesthesia (‘preoxygenation’), then alveolar gas behind closed airways contains little or no nitrogen and will collapse within a few minutes causing atelectasis. With increasing alveolar nitrogen concentrations, the time to collapse is increasingly prolonged, and with room air present in the alveoli (79% nitrogen),
the collapse takes a couple of hours. Regions behind intermittently closed airways may also collapse, depending upon the degree that alveolar ventilation is impaired. ˙ ratio will even˙ Q Thus, a region with a low enough V= tually collapse and cause shunt.3 The fall in FRC occurs promptly during induction of general anaesthesia, and with preoxygenation with 100% oxygen, atelectasis occurs within a few minutes and remains present throughout anaesthesia, as does the resultant shunt. This atelectasis may persist in the postoperative period for some days after upper abdominal ˙ will mostly parallel the presence of ˙ Q surgery. Low V= atelectasis and shunt, but the amount of each may vary between individuals. Airway closure is a normal phenomenon and can be seen in healthy individuals after maximal expiration. The propensity for airway closure increases with age due to cumulative loss of elastic tissue in the lung. Airway closure rarely occurs even after maximal expiratory effort at an age of around 20 yr, but with increasing age may occur within a normal breath in 40 to 50-year-old supine individuals and can be seen above FRC in upright 70-year-old individuals.2 An intermittent deep inspiration opens up the otherwise closed airways and refills the shrinking alveoli. Interestingly, children suffer more from airway closure than young adults and the smaller the child the greater the degree of airway closure. This is thought to be related to the developing lung.4 ˙ is age-dependent and very ˙ Q During anaesthesia, a low V= little can be seen in patients below an age of 40 to 50 yr. Atelectasis and accompanying shunt, on the contrary, appear not to be age-dependent5 as one would expect. This may be because preoxygenation of the elderly requires a longer period of time to achieve 100% alveolar oxygen than in younger individuals and this time may not be allowed for. That is, a slower filling of alveoli with oxygen may slightly reduce the atelectasis that ensues. Whether this can be considered a protective effect in the older patient is open to discussion. The net effect is that
From the Department of Medical Sciences, Clinical Physiology, Uppsala University Hospital, Uppsala, Sweden Correspondence to Go¨ran Hedenstierna, Department of Medical Sciences, Clinical Physiology, Uppsala University Hospital, 75185 Uppsala, Sweden Tel: +46 186114144; fax: +46 186114153; e-mail: [email protected] 0265-0215 ß 2014 Copyright European Society of Anaesthesiology
DOI:10.1097/EJA.0000000000000102
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
448 Hedenstierna
atelectasis, in proportion to lung size, occurs to a similar degree in the neonate as in the older patient during anaesthesia. With the exception of ketamine,6 all general anaesthetics, whether inhalational or intravenous, cause more or less the same fall in FRC as well as atelectasis with shunt and ˙ Ketamine preserves muscle ˙ Q. airway closure with low V= tone, does not lower FRC and does not cause atelectasis or shunt. However, if a muscle relaxant is given to a patient during ketamine anaesthesia, then atelcectasis and shunt ensue. These findings emphasise that there are two major causes of gas exchange impairment during anaesthesia: a reduction in FRC and a high inspired oxygen concentration. One must not forget the weakening of the hypoxic pulmonary vasoconstriction (HPV) that most anaesthetics cause, with inhalational agents possibly blunting HPV to a greater degree than intravenous anaesthetics.7 However, the alveolar concentrations involved are too low to have considerable impact and will not be discussed in any detail here. Other considerations are the effect of coexisting diseases and different anaesthetic and surgical procedures. Again, there is not space enough here to deal with these issues, but the interested reader is referred to the review article of Hedenstierna and Rothen.8 ˙ matching ˙ Q Different steps can be taken to improve V= and will be discussed as follows: (1) The application of 10 cmH2O positive end-expiratory pressure (PEEP) reopens collapsed lung tissue. This is more likely an effect of increased inspiratory airway pressure than that of PEEP per se.8,9 Higher PEEP may be needed in some patients of normal weight but is of particular value in the profoundly obese patient. Limited knowledge exists as to what the optimum PEEP is in this respect. Shunt is not reduced proportionately by this manoeuvre and arterial oxygenation may not improve. This may be explained by a redistribution of blood flow towards more dependent, still atelectatic parts of the lungs and a decrease in cardiac output. The lung recollapses rapidly (within 1 min) following discontinuation of PEEP. Preventing the fall in FRC during induction using continuous positive airway pressure (CPAP), followed by PEEP is another preventive measure.10 (2) A ‘sigh’ manoeuvre, or double tidal volume, has been suggested to open collapsed lung areas and improve gas exchange, both for intubated and nonintubated patients.11 The amount of atelectasis, however, does not change during normal tidal breathing or by a ‘sigh’ using an airway pressure of up to 20 cmH2O. To reopen all collapsed lung tissue in anaesthetised adults with healthy lungs, an airway pressure of 40 cmH2O maintained for 10 s is required. Lung inflation such as this corresponds to a maximum spontaneous inspiration in the awake, supine patient
and may be called a ‘vital capacity manoeuvre’ (or recruitment manoeuvre). High inspiratory pressures may cause transient haemodynamic instability with associated side effects, especially in hypovolaemic individuals. In addition, alveolar expansion may occur in a nonuniform fashion, resulting in local alveolar overdistension, even at lower recruitment pressures.12 (3) Preoxygenation is undertaken to prevent hypoxaemia in the event of difficult tracheal intubation and will, for the anaesthetist, be an important procedure to ensure maximum safety. However, the potential for development of atelectasis should be also be a consideration, as this too will shorten the ‘apnoea tolerance time’ - the time before hypoxaemia develops. Preoxygenation with lower inspired oxygen concentrations reduces atelectasis but at the cost of a shortened ‘apnoea tolerance time’.13 Although using 80% oxygen for preoxygenation results in less atelectasis, one must be aware that the reduction in atelectasis is only temporary; it will increase to the same size as with preoxygenation with 100% oxygen after 30 min.14 However, this gives time to intervene with a recruitment manoeuvre using a lower oxygen concentration and this should prevent further collapse. (4) Oxygenation during ongoing anaesthesia: ventilation of the lungs with 100% oxygen after a ‘vital capacity manoeuvre’ that had reopened previously collapsed lung tissue results in a rapid reappearance of the atelectasis. If, on the contrary, 40% oxygen in nitrogen is used for ventilation of the lungs, atelectasis reappears more slowly. Thus, to prevent atelectasis and shunt, ventilation during anaesthesia should be done with a moderate fraction of inspired oxygen (e.g. 30 to 40%) and be increased only if arterial oxygenation is compromised.10 (5) Postoxygenation: another situation wherein a high oxygen concentration is used is at the end of the anaesthesia. A postoxygenation manoeuvre is regularly performed to reduce the risk of hypoxaemia during awakening. This is mostly done in combination with airway suctioning to eliminate secretions. However, the combination of postoxygenation and airway suctioning is the most effective method of producing atelectasis and shunt in the anaesthetised patient. A recruitment manoeuvre after postoxygenation and suctioning, followed by ventilation with a lower oxygen concentration, seems to be effective in preventing alveolar recollapse.15 In summary, general anaesthesia lowers FRC thereby promoting airway closure and absorbtion atelectasis, the ˙ and the latter shunt. Together, ˙ Q former causing low V= these two physiological disturbances account for around 75% of the impairment of oxygenation during ‘uneventful’ anaesthesia. General anaesthetics blunt HPV but to a
Eur J Anaesthesiol 2014; 31:447–449 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
Effects of anaesthesia on ventilation/perfusion matching 449
limited degree and would have no effect at all on gas ˙ match. Preventing ˙ Q exchange if there was a normal V= the fall in FRC by CPAP or PEEP, opening up collapsed alveoli by recruitment manoeuvres and using moderate inspired oxygen concentrations are measures to keep ˙ matching ˙ Q lung units open and to ensure acceptable V= and gas exchange.
5
Acknowledgements relating to this article
9
6
7 8
Assistance with the editorial: none. Financial support and sponsorship: supported by grants from the Swedish research Council, 5315, and Uppsala University. Conflicts of interest: none. Comment from the Editor: this article was checked and accepted by the Editors, but was not sent for external peer-review.
References 1 2 3 4
Wahba RWM. Perioperative functional residual capacity. Can J Anaesth 1991; 38:384–400. Milic-Emili J, Torchio R, D’Angelo E. Closing volume: a reappraisal (1967– 2007). Eur J Appl Physiol 2007; 99:567–583. Dantzker DR, Wagner PD, West JB. Instability of lung units with low VA/Q ratios during O2 breathing. J Appl Physiol 1975; 38:886–895. Mansell A, Bryan C, Levison H. Airway closure in children. J Appl Physiol 1972; 33:711–714.
10
11
12 13
14
15
Gunnarsson L, Tokics L, Gustavsson H, Hedenstierna G. Influence of age on atelectasis formation and gas-exchange impairment during generalanesthesia. Br J Anaesth 1991; 66:423–432. Tokics L, Strandberg A˚, Brismar B, et al. Computerized tomography of the chest and gas exchange measurements during ketamine anesthesia. Acta Anesthesiol Scand 1987; 31:684–692. Sylvester JT, Shimoda LA, Aaronson PI, Ward JP. Hypoxic pulmonary vasoconstriction. Physiol Rev 2012; 92:367–520. Hedenstierna G, Rothen HU. Respiratory function during anesthesia: effects on gas exchange. American Physiological Society. Compr Physiol 2012; 2:69–96. Hedenstierna G. Oxygen and anesthesia: what lung do we deliver to the postoperative ward? Acta Anaesthesiol Scand 2012; 56:675– 685. Rusca M, Proietti S, Schnyder P, et al. Prevention of atelectasis formation during induction of general anesthesia. Anesth Analg 2003; 97:1835– 1839. Scholten DJ, Novak R, Snyder JV. Directed manual recruitment of collapsed lung in intubated and nonintubated patients. Am Surg 1985; 51:330–335. Perlman CE, Bhattacharya J. Alveolar expansion imaged by optical sectioning microscopy. J Appl Physiol 2007; 103:1037–1044. Edmark L, Kostova-Aherdan K, Enlund M, Hedenstierna G. Optimal oxygen concentration during induction of general anesthesia. Anesthesiology 2003; 98:28–33. Edmark L, Auner U, Enlund M, et al. Oxygen concentration and characteristics of progressive atelectasis formation during anaesthesia. Acta Anaesthesiol Scand 2011; 55:75–81. Benoıˆt Z, Wicky S, Fischer JF, et al. The effect of increased FIO(2) before tracheal extubation on postoperative atelectasis. Anesth Analg 2002; 95:1472–1473.
Eur J Anaesthesiol 2014; 31:447–449 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
EDITORIAL
Effects of anaesthesia on ventilation/perfusion matching Go¨ran Hedenstierna
European Journal of Anaesthesiology 2014, 31:447–449
Almost all general anaesthetics cause a loss of muscle tone. This does not preclude spontaneous respiratory efforts, but the static tone is reduced. The balance between inward forces (lung recoil) and outward forces (chest wall expansion) at the resting volume, namely functional residual capacity (FRC), is altered, with a decrease in the outward forces so that resting lung volume is reduced. The shift from upright to supine reduces FRC by approximately 0.7 to 0.8 l and general anaesthesia by a further 0.4 to 0.5 l.1 FRC is now close to residual volume - the volume reached by a maximum expiration. At this lung volume, airways in lower, dependent lung regions close during expiration. Some airways may open up during the next inspiration, however, with reduced ventilation in the subtended lung region and subsequent reduction in ventilation/perfusion ratios ˙ Other airways further down the bronchial tree, ˙ Q). (V= may stay closed during the whole breath and the subtended alveoli are not ventilated, causing shunt. The reason for the gravitational distribution of airway closure is the increasing pleural pressure down the pleural space, being negative in the upper region (apex in upright and anterior in supine position) and positive in dependent regions after a deep expiration.2 The oxygen in the gas trapped behind closed airways will rapidly be absorbed by the capillary blood flow and will not be replenished by gas from the outside via the trachea. Carbon dioxide is delivered to the alveoli from the blood, but diffuses easily into the lung tissue and the volume is normally smaller than the amount of oxygen absorbed. The alveoli shrink but are kept open by any remaining nitrogen. If ventilation is provided with 100% oxygen during the induction of anaesthesia (‘preoxygenation’), then alveolar gas behind closed airways contains little or no nitrogen and will collapse within a few minutes causing atelectasis. With increasing alveolar nitrogen concentrations, the time to collapse is increasingly prolonged, and with room air present in the alveoli (79% nitrogen),
the collapse takes a couple of hours. Regions behind intermittently closed airways may also collapse, depending upon the degree that alveolar ventilation is impaired. ˙ ratio will even˙ Q Thus, a region with a low enough V= tually collapse and cause shunt.3 The fall in FRC occurs promptly during induction of general anaesthesia, and with preoxygenation with 100% oxygen, atelectasis occurs within a few minutes and remains present throughout anaesthesia, as does the resultant shunt. This atelectasis may persist in the postoperative period for some days after upper abdominal ˙ will mostly parallel the presence of ˙ Q surgery. Low V= atelectasis and shunt, but the amount of each may vary between individuals. Airway closure is a normal phenomenon and can be seen in healthy individuals after maximal expiration. The propensity for airway closure increases with age due to cumulative loss of elastic tissue in the lung. Airway closure rarely occurs even after maximal expiratory effort at an age of around 20 yr, but with increasing age may occur within a normal breath in 40 to 50-year-old supine individuals and can be seen above FRC in upright 70-year-old individuals.2 An intermittent deep inspiration opens up the otherwise closed airways and refills the shrinking alveoli. Interestingly, children suffer more from airway closure than young adults and the smaller the child the greater the degree of airway closure. This is thought to be related to the developing lung.4 ˙ is age-dependent and very ˙ Q During anaesthesia, a low V= little can be seen in patients below an age of 40 to 50 yr. Atelectasis and accompanying shunt, on the contrary, appear not to be age-dependent5 as one would expect. This may be because preoxygenation of the elderly requires a longer period of time to achieve 100% alveolar oxygen than in younger individuals and this time may not be allowed for. That is, a slower filling of alveoli with oxygen may slightly reduce the atelectasis that ensues. Whether this can be considered a protective effect in the older patient is open to discussion. The net effect is that
From the Department of Medical Sciences, Clinical Physiology, Uppsala University Hospital, Uppsala, Sweden Correspondence to Go¨ran Hedenstierna, Department of Medical Sciences, Clinical Physiology, Uppsala University Hospital, 75185 Uppsala, Sweden Tel: +46 186114144; fax: +46 186114153; e-mail: [email protected] 0265-0215 ß 2014 Copyright European Society of Anaesthesiology
DOI:10.1097/EJA.0000000000000102
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
448 Hedenstierna
atelectasis, in proportion to lung size, occurs to a similar degree in the neonate as in the older patient during anaesthesia. With the exception of ketamine,6 all general anaesthetics, whether inhalational or intravenous, cause more or less the same fall in FRC as well as atelectasis with shunt and ˙ Ketamine preserves muscle ˙ Q. airway closure with low V= tone, does not lower FRC and does not cause atelectasis or shunt. However, if a muscle relaxant is given to a patient during ketamine anaesthesia, then atelcectasis and shunt ensue. These findings emphasise that there are two major causes of gas exchange impairment during anaesthesia: a reduction in FRC and a high inspired oxygen concentration. One must not forget the weakening of the hypoxic pulmonary vasoconstriction (HPV) that most anaesthetics cause, with inhalational agents possibly blunting HPV to a greater degree than intravenous anaesthetics.7 However, the alveolar concentrations involved are too low to have considerable impact and will not be discussed in any detail here. Other considerations are the effect of coexisting diseases and different anaesthetic and surgical procedures. Again, there is not space enough here to deal with these issues, but the interested reader is referred to the review article of Hedenstierna and Rothen.8 ˙ matching ˙ Q Different steps can be taken to improve V= and will be discussed as follows: (1) The application of 10 cmH2O positive end-expiratory pressure (PEEP) reopens collapsed lung tissue. This is more likely an effect of increased inspiratory airway pressure than that of PEEP per se.8,9 Higher PEEP may be needed in some patients of normal weight but is of particular value in the profoundly obese patient. Limited knowledge exists as to what the optimum PEEP is in this respect. Shunt is not reduced proportionately by this manoeuvre and arterial oxygenation may not improve. This may be explained by a redistribution of blood flow towards more dependent, still atelectatic parts of the lungs and a decrease in cardiac output. The lung recollapses rapidly (within 1 min) following discontinuation of PEEP. Preventing the fall in FRC during induction using continuous positive airway pressure (CPAP), followed by PEEP is another preventive measure.10 (2) A ‘sigh’ manoeuvre, or double tidal volume, has been suggested to open collapsed lung areas and improve gas exchange, both for intubated and nonintubated patients.11 The amount of atelectasis, however, does not change during normal tidal breathing or by a ‘sigh’ using an airway pressure of up to 20 cmH2O. To reopen all collapsed lung tissue in anaesthetised adults with healthy lungs, an airway pressure of 40 cmH2O maintained for 10 s is required. Lung inflation such as this corresponds to a maximum spontaneous inspiration in the awake, supine patient
and may be called a ‘vital capacity manoeuvre’ (or recruitment manoeuvre). High inspiratory pressures may cause transient haemodynamic instability with associated side effects, especially in hypovolaemic individuals. In addition, alveolar expansion may occur in a nonuniform fashion, resulting in local alveolar overdistension, even at lower recruitment pressures.12 (3) Preoxygenation is undertaken to prevent hypoxaemia in the event of difficult tracheal intubation and will, for the anaesthetist, be an important procedure to ensure maximum safety. However, the potential for development of atelectasis should be also be a consideration, as this too will shorten the ‘apnoea tolerance time’ - the time before hypoxaemia develops. Preoxygenation with lower inspired oxygen concentrations reduces atelectasis but at the cost of a shortened ‘apnoea tolerance time’.13 Although using 80% oxygen for preoxygenation results in less atelectasis, one must be aware that the reduction in atelectasis is only temporary; it will increase to the same size as with preoxygenation with 100% oxygen after 30 min.14 However, this gives time to intervene with a recruitment manoeuvre using a lower oxygen concentration and this should prevent further collapse. (4) Oxygenation during ongoing anaesthesia: ventilation of the lungs with 100% oxygen after a ‘vital capacity manoeuvre’ that had reopened previously collapsed lung tissue results in a rapid reappearance of the atelectasis. If, on the contrary, 40% oxygen in nitrogen is used for ventilation of the lungs, atelectasis reappears more slowly. Thus, to prevent atelectasis and shunt, ventilation during anaesthesia should be done with a moderate fraction of inspired oxygen (e.g. 30 to 40%) and be increased only if arterial oxygenation is compromised.10 (5) Postoxygenation: another situation wherein a high oxygen concentration is used is at the end of the anaesthesia. A postoxygenation manoeuvre is regularly performed to reduce the risk of hypoxaemia during awakening. This is mostly done in combination with airway suctioning to eliminate secretions. However, the combination of postoxygenation and airway suctioning is the most effective method of producing atelectasis and shunt in the anaesthetised patient. A recruitment manoeuvre after postoxygenation and suctioning, followed by ventilation with a lower oxygen concentration, seems to be effective in preventing alveolar recollapse.15 In summary, general anaesthesia lowers FRC thereby promoting airway closure and absorbtion atelectasis, the ˙ and the latter shunt. Together, ˙ Q former causing low V= these two physiological disturbances account for around 75% of the impairment of oxygenation during ‘uneventful’ anaesthesia. General anaesthetics blunt HPV but to a
Eur J Anaesthesiol 2014; 31:447–449 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
Effects of anaesthesia on ventilation/perfusion matching 449
limited degree and would have no effect at all on gas ˙ match. Preventing ˙ Q exchange if there was a normal V= the fall in FRC by CPAP or PEEP, opening up collapsed alveoli by recruitment manoeuvres and using moderate inspired oxygen concentrations are measures to keep ˙ matching ˙ Q lung units open and to ensure acceptable V= and gas exchange.
5
Acknowledgements relating to this article
9
6
7 8
Assistance with the editorial: none. Financial support and sponsorship: supported by grants from the Swedish research Council, 5315, and Uppsala University. Conflicts of interest: none. Comment from the Editor: this article was checked and accepted by the Editors, but was not sent for external peer-review.
References 1 2 3 4
Wahba RWM. Perioperative functional residual capacity. Can J Anaesth 1991; 38:384–400. Milic-Emili J, Torchio R, D’Angelo E. Closing volume: a reappraisal (1967– 2007). Eur J Appl Physiol 2007; 99:567–583. Dantzker DR, Wagner PD, West JB. Instability of lung units with low VA/Q ratios during O2 breathing. J Appl Physiol 1975; 38:886–895. Mansell A, Bryan C, Levison H. Airway closure in children. J Appl Physiol 1972; 33:711–714.
10
11
12 13
14
15
Gunnarsson L, Tokics L, Gustavsson H, Hedenstierna G. Influence of age on atelectasis formation and gas-exchange impairment during generalanesthesia. Br J Anaesth 1991; 66:423–432. Tokics L, Strandberg A˚, Brismar B, et al. Computerized tomography of the chest and gas exchange measurements during ketamine anesthesia. Acta Anesthesiol Scand 1987; 31:684–692. Sylvester JT, Shimoda LA, Aaronson PI, Ward JP. Hypoxic pulmonary vasoconstriction. Physiol Rev 2012; 92:367–520. Hedenstierna G, Rothen HU. Respiratory function during anesthesia: effects on gas exchange. American Physiological Society. Compr Physiol 2012; 2:69–96. Hedenstierna G. Oxygen and anesthesia: what lung do we deliver to the postoperative ward? Acta Anaesthesiol Scand 2012; 56:675– 685. Rusca M, Proietti S, Schnyder P, et al. Prevention of atelectasis formation during induction of general anesthesia. Anesth Analg 2003; 97:1835– 1839. Scholten DJ, Novak R, Snyder JV. Directed manual recruitment of collapsed lung in intubated and nonintubated patients. Am Surg 1985; 51:330–335. Perlman CE, Bhattacharya J. Alveolar expansion imaged by optical sectioning microscopy. J Appl Physiol 2007; 103:1037–1044. Edmark L, Kostova-Aherdan K, Enlund M, Hedenstierna G. Optimal oxygen concentration during induction of general anesthesia. Anesthesiology 2003; 98:28–33. Edmark L, Auner U, Enlund M, et al. Oxygen concentration and characteristics of progressive atelectasis formation during anaesthesia. Acta Anaesthesiol Scand 2011; 55:75–81. Benoıˆt Z, Wicky S, Fischer JF, et al. The effect of increased FIO(2) before tracheal extubation on postoperative atelectasis. Anesth Analg 2002; 95:1472–1473.
Eur J Anaesthesiol 2014; 31:447–449 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
