Medication compliance in asthma is disappointingly low and leads to poor asthma control in children. It is very common that parents do not supervise treatment and often report poor asthma control. Many difficult-to-manage asthmatics have ongoing exposure to allergens or other asthma
triggers. In such instances, required medication may be very high and the results may be disappointing. Only 30% of pediatric a...
Medication compliance in asthma is disappointingly low and leads to poor asthma control in children. It is very common that parents do not supervise treatment and often report poor asthma control. Many difficult-to-manage asthmatics have ongoing exposure to allergens or other asthma
triggers. In such instances, required medication may be very high and the results may be disappointing. Only 30% of pediatric asthmatics, age 7 to 15, have optimal environmental control at home. Children who are
nonadherent to both medications and environmental control measures can be challenging to manage.
Despite the fact that many immunologic abnormalities have been identified, there is no laboratory test that can be used in making the diagnosis of steroid-resistant asthma. As a result the diagnosis of steroid-resistant asthma remains a clinical one.
We would like to thank Dr Molloy for her interest in our recent paper showing delayed neutrophil apoptosis in infants who progressed to chronic lung disease prematurity (CLD) and indeed in those infants who do not survive their course of extracorporeal membrane oxygenation (ECMO) for
severe respiratory failure.[1] Having established the association, we
are now exploring the potential mechanisms that mi...
We would like to thank Dr Molloy for her interest in our recent paper showing delayed neutrophil apoptosis in infants who progressed to chronic lung disease prematurity (CLD) and indeed in those infants who do not survive their course of extracorporeal membrane oxygenation (ECMO) for
severe respiratory failure.[1] Having established the association, we
are now exploring the potential mechanisms that might result in delayed
neutrophil apoptosis in infants who develop CLD. Dr Molloy mentions in
her letter a number of important clinical factors that might influence
rates of neutrophil apoptosis in new born children. The principal aim of
our study, however, was to determine whether or not there were differences
in
neutrophil apoptosis between CLD babies and those who recover from RDS.
We refrained from over analysing the data, since far greater numbers would
need to be studied to establish the effects of other co-morbidities,
maternal factors and ventilatory parameters on the outcomes we measured.
Nonetheless we entirely agree with Dr Molloy that many of the factors she mentions, both perinatal factors such as chorioamnionitis and mode of delivery, and post natal factors such as mechanical ventilation have the potential to influence pulmonary inflammation and neutrophil apoptosis.
Ultimately, whether any of these factors have a direct causal role might
need to be
addressed in other systems such as animal models.
The small amounts of BAL obtained from the babies studied limited the cytokine analyses we were able to perform. We did not measure IL-6 in this cohort. Measurements of GCSF were available in a proportion of the babies. Although GCSF levels were raised in some of the babies there was no clear association with development of CLD.
Sailesh Kotecha Child Health, University of Leicester
Moira Whyte
Respiratory Medicine, University of Sheffield
Reference
S Kotecha, R J Mildner, L R Prince, J R Vyas, A E Currie, R A Lawson, and M K B Whyte. The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants. Thorax 2003; 58: 961-967.
We thank Dr Agarwal for responding to our article. We agree that the
commonest cause of steroid resistant asthma is failure to take the
prescribed steroids. However, there are perhaps more diagnostic aids than
is acknoweldged. Compliance can be taken out of the equation by doing a
therapeutic trial of a single intramuscular injection of depot
triamcinolone.[1-4] If asthma persists, then it can truly be...
We thank Dr Agarwal for responding to our article. We agree that the
commonest cause of steroid resistant asthma is failure to take the
prescribed steroids. However, there are perhaps more diagnostic aids than
is acknoweldged. Compliance can be taken out of the equation by doing a
therapeutic trial of a single intramuscular injection of depot
triamcinolone.[1-4] If asthma persists, then it can truly be said to be
steroid resistant. Alternatively, measuring serum prednisolone and
cortisol levels may also be illuminating, if the child is supposedly
taking oral steroids.
References
(1) Veeraraghavan S, Sharma OP. Parenteral triamcinolone acetonide:
an alternative corticosteroid for the treatment of asthma. Curr Opin Pulm
Med 1998;4:31-5.
(2) McLeod DT, Capewell SJ, Law J, MacLaren W, Seaton A.
Intramuscular triamcinolone acetonide in chronic severe asthma. Thorax
1985;40:840-5.
(3) Willey RF, Fergusson RJ, Godden DJ, Crompton GK, Grant IW. Comparison
of oral prednisolone and intramuscular depot triamcinolone in patients
with severe chronic asthma. Thorax 1984;39:340-4.
(4) Ogirala RG, Aldrich TK, Prezant DJ, Sinnett MJ, Enden JB,
Williams MH Jr. High-dose intramuscular triamcinolone in severe, chronic,
life-threatening asthma. N Engl J Med 1991;324:585-9.
We agree with Dr Anderson in that patterns of alcohol consumption may
vary amongst social class. Nevertheless, in our investigation, most of the
people were of low-middle social class. In Spain it is possible that,
independently of the economic position, people can have the same access
to alcohol since it can be obtained at various prices (from 1€ per bottle
to 20€ or more for red wine). The same is...
We agree with Dr Anderson in that patterns of alcohol consumption may
vary amongst social class. Nevertheless, in our investigation, most of the
people were of low-middle social class. In Spain it is possible that,
independently of the economic position, people can have the same access
to alcohol since it can be obtained at various prices (from 1€ per bottle
to 20€ or more for red wine). The same is true for white wine. It should
be kept in mind that although the price is different, the composition is
essentially the same. Based on these assumptions we think that in our
particular case, the pattern of wine consumption is not altered by the
social class.
Evidence that self management programmes for asthma are effective in
primary care is elusive.[1] Thoonen and colleagues have carried out a
complex and impressive cluster randomised trial from which they conclude
that a
self management programme implemented in Dutch general practices lowers
the burden of illness.[2] Parts of their analysis require comment.
Evidence that self management programmes for asthma are effective in
primary care is elusive.[1] Thoonen and colleagues have carried out a
complex and impressive cluster randomised trial from which they conclude
that a
self management programme implemented in Dutch general practices lowers
the burden of illness.[2] Parts of their analysis require comment.
It is not
clear whether clustering has been taken into account in the analysis.[3]
This could materially affect the conclusions of the study. The main
difference observed between groups was in the percentage of successfully
treated weeks. This is an unusual and unvalidated outcome measure and it
would be of interest to know if its method of analysis was pre-specified
in the trial protocol. Although changes in quality of life (on which the
power calculation was based) approached statistical significance they were
rather far from being clinically significant. Given that there were no
changes in exacerbation frequency, lung function or health service use it
would seem that benefits are at best marginal.
Primary care clinicians
continue to devote considerable resources to providing self management
advice to their patients but proof of substantial benefits remains
difficult to demonstrate.
References
(1) Fay JK, Jones A and Ram FSF Primary care based
clinics for asthma (Cochrane Review). The Cochrane Library (Issue 4).
2002. Oxford: Update Software.
(2) Thoonen BPA, Schermer TRJ, van den Boom G, Molema J, Folgering H,
Akkermans RP et al. Self-management of asthma in general practice, asthma
control and quality of life: a randomised controlled trial. Thorax 2003;58:30-6.
(3) Campbell MK, Mollison J, Steen N, Grimshaw J, Eccles M. Analysis
of cluster randomised trials in primary care: a practical approach. Fam Pract 2000;17:192-6.
The acute respiratory distress syndrome (ARDS) was first described in
1967, when Ashbaugh and colleagues reported 12 patients with acute
respiratory distress, cyanosis refractory to oxygen therapy, decreased
lung compliance and diffuse pulmonary infiltrates on the chest radiograph
(1). In 1994, new definition was recommended by the American-European
Consensus Conference that has been widely accepted by...
The acute respiratory distress syndrome (ARDS) was first described in
1967, when Ashbaugh and colleagues reported 12 patients with acute
respiratory distress, cyanosis refractory to oxygen therapy, decreased
lung compliance and diffuse pulmonary infiltrates on the chest radiograph
(1). In 1994, new definition was recommended by the American-European
Consensus Conference that has been widely accepted by clinicians and
research workers. Acute lung injury (ALI) is defined as a syndrome of
acute and persistent lung inflammation with increased vascular
permeability. It is characterized by a ratio of the partial pressure of
arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) of 300 or
less, regardless of the level of PEEP, bilateral pulmonary infiltrates on
the chest radiograph and the absence of clinical evidence of elevated left
atrial pressure or if measured, the pulmonary capillary wedge pressure
(PCWP) of 18 mm Hg or less. The definition of ARDS is exactly the same
except that the hypoxemia is more severe with a PaO2 to FiO2 ratio of 200
or less, regardless of the level of PEEP (2).
Mechanical ventilation is a life-saving therapy that has become the
mainstay of management of patients with ARDS. Traditionally, the adverse
consequences of mechanical ventilation include hypotension from reduced
venous return and barotrauma with pneumothorax, pneumomediastinum and
rarely air embolism. More recently, various studies have shown less
obvious and perhaps more dangerous types of ventilator-induced lung
injury, including volutrauma, atelectrauma and biotrauma (3). Volutrauma
is a more subtle type of lung injury that can occur secondary to alveolar
overdistension when large tidal volumes and/or excessive PEEP are used.
The term volutrauma indicates that it is the lung volume rather than the
airway pressure that causes this type of lung injury (4). Cyclical
atelectasis or atelectrauma refers to the damage that can occur when the
lungs become atelectatic during expiration and re-expanded on inspiration,
particularly when low levels of PEEP are applied (5). Biotrauma is
characterized by the release of inflammatory mediators from the injured
lungs into the systemic circulation. These mediators can promote further
lung injury and contribute to the development of multi-organ failure,
particularly during traditional tidal volume ventilation (10 to 15 mL/Kg
of ideal body weight) (6). The concept of biotrauma may explain why the
mortality of ARDS remains high (about 50 percent), despite the great
advances in mechanical ventilation, as most patients die of multi-organ
failure rather than respiratory failure (7).
For most patients with ARDS, high levels of FiO2 and PEEP are required to
achieve satisfactory arterial oxygenation. Unfortunately, both of these
treatments have potential adverse effects that must be carefully
considered in individual patients. A spectrum of lung injury, ranging from
mild tracheobronchitis to diffuse alveolar damage which is histologically
indistinguishable from ARDS, may result from high concentrations of
inspired oxygen (8). In general, an FiO2 of 0.6 or less is usually
considered to be safe. However, the diseased lungs, in ARDS, may be more
susceptible to oxygen toxicity at a relatively low FiO2 (9).
Permissive hypoxemia indicates that arterial oxygen saturation below 90
percent can be accepted, as long as there is no evidence of tissue
hypoxia. We can therefore, avoid the application of high FiO2 and/or
excessive PEEP that can induce pulmonary oxygen toxicity, barotrauma,
volutrauma and contribute to multi-organ failure. It must be emphasised
that even safe levels of FiO2 (equal to or less than 0.6) can cause oxygen
toxicity and promote further lung injury, that can be difficult to
diagnose in the clinical setting of ARDS. Permissive hypoxemia illustrates
the importance of tissue oxygenation rather than arterial oxygen
saturation as a goal of therapy of patients with ARDS. On the contrary,
conventional ventilatory strategies for patients with ARDS focus on
maintaining adequate arterial oxygenation (SaO2 around 90 percent)
assuming that lower levels of SaO2 would compromise tissue oxygenation and
lead to tissue hypoxia. However, the relationship between arterial oxygen
saturation and oxygen delivery is not always parallel as it is not only
the saturation of hemoglobin, but also hemoglobin affinity that determines
the amount of oxygen released to the tissues. Hemoglobin affinity for
oxygen changes according to variations in pH, partial pressure of arterial
carbon dioxide (PaCO2), temperature and red-cell 2,3-diphosphoglycerate
(2,3 DPG). In patients with acidosis or hypercapnia, hemoglobin affinity
is decreased and oxygen dissociation curve is shifted to the right,
facilitating the release of oxygen to the tissues (10). Therefore, SaO2
may be relatively low, in spite of improved oxygen delivery to the
tissues, raising a concern about arterial oxygen saturation as an
indicator of tissue oxygenation. As a result of the widely used lung-
protective ventilation, many patients with ARDS are now prone to develop
hypercapnia and respiratory acidosis (permissive hypercapnia), that can
promote oxygen delivery and improve tissue oxygenation, regardless of the
relatively low arterial oxygen saturation. During permissive hypercapnia,
the relatively low SaO2 for a given PaO2 may lead to unnecessary increase
in FiO2 and/or PEEP that can be particularly deleterious to patients with
ARDS. Permissive hypoxemia therefore, has the theoretical advantage of
reducing the risk of pulmonary oxygen toxicity, barotrauma, alveolar
overdistension and multi-organ failure without necessarily compromising
tissue oxygenation, especially in the adequately sedated and paralysed
patients.
Arterial hypoxemia may compromise oxygen delivery and lead to tissue
hypoxia, especially when accompanied by decreased cardiac output, low
hemoglobin concentration or increased metabolic demands of the body.
However, to what extent is tissue hypoxia implicated in the pathogenesis
of multi-organ failure and death in patients with ARDS? Surprisingly,
tissue hypoxia probably contributes only a little to the pathogenesis of
multi-organ failure. The release of inflammatory mediators into the
systemic circulation, as a result of alveolar overdistension may
contribute to the development of multi-organ failure and death in ARDS
patients (6). The concept of biotrauma, rather than tissue hypoxia may
explain why multi-organ failure, rather than hypoxemia is the major cause
of death of ARDS. In the absence of tissue hypoxia, permissive hypoxemia
may be more safe than increasing the FiO2 and/or PEEP, which can induce
pulmonary oxygen toxicity, alveolar overdistension and multi-organ
failure, in spite of maintaining adequate arterial oxygenation. I may
therefore, hypothesize that maintaining the SaO2 at 90 percent or more
through the application of relatively high FiO2 or PEEP can be more
dangerous than permissive hypoxemia, as long as it has not resulted in
significant tissue hypoxia.
Tissue oxygenation reflects the balance between oxygen delivery (DO2) and
oxygen consumption (VO2). Tissue hypoxia can develop if there is a
decrease in DO2, as in shock, hypoxemia or severe anemia or increase in
VO2, as a result of increased metabolic demands of the body (11). Tissue
oxygenation is not determined by arterial oxygen saturation alone, other
factors include cardiac output, hemoglobin concentration, oxygen affinity
of hemoglobin and oxygen demand of the body. It must be emphasised that
the body can remarkably tolerate hypoxemia by a compensatory increase in
blood flow and oxygen extraction ratio (12). I may therefore, speculate
that permissive hypoxemia is not necessarily accompanied by significant
tissue hypoxia, particularly if the other parameters of oxygen delivery,
such as cardiac output and hemoglobin concentration are normalized and
oxygen consumption is minimized by the appropriate use of sedation,
analgesia and muscle paralysis. Because of the sigmoid shape of oxygen
dissociation curve, once the PaO2 has reached 60 mm Hg, further decrease
in PaO2, will result in dramatic fall in arterial oxygen saturation. When
the PaO2 is allowed to decrease below 60 mm Hg, as in permissive
hypoxemia, the dissociation curve becomes very steep reflecting the low
oxygen affinity of hemoglobin that enhances the release of oxygen to the
tissues, in spite of the low arterial oxygen saturation. Permissive
hypoxemia may therefore, favour oxygen unloading at the tissues by
reducing hemoglobin affinity for oxygen. At a PaO2 of 60 mm Hg, the
dissociation curve is almost flat indicating that further increase in PaO2
will have little effect on arterial oxygen saturation (13). Hence, a PaO2
of 60 mm Hg or SaO2 of 90 percent has been considered as an index of
adequate arterial oxygenation in most ventilatory strategies of ARDS.
However, lower levels of PaO2 or SaO2 may not necessarily lead to
significant tissue hypoxia, because of the decrease in oxygen affinity of
hemoglobin that favours peripheral oxygen unloading, increase in oxygen
extraction and reduction in metabolic demand and oxygen consumption in the
ventilated, sedated and paralyzed patients.
Mild pulmonary hypertension is frequently seen in patients with ARDS. In
some patients, acute cor pulmonale and right ventricular dysfunction can
develop (14). Inhaled nitric oxide is a potent pulmonary vasodilator, that
can be used in some patients with refractory hypoxemia or severe pulmonary
hypertension, without causing systemic vasodilatation (15). During
permissive hypoxemia, especially when relatively low levels of PaO2 are
allowed, continuous hemodynamic monitoring of pulmonary artery pressure,
with Swan-Ganz catheter is important to detect clinically significant
pulmonary hypertension that may require treatment with inhaled nitric
oxide or prostacyclin.
Cardiac index greater than 4.5 liters per minute per square meter of body
surface area is commonly referred to as supra-normal cardiac output. I may
hypothesize that oxygen delivery can be maintained within normal or near-
normal value by augmenting cardiac output to compensate for the low
arterial oxygen saturation. Maintaining supra-normal cardiac output can
therefore, reduce tissue hypoxia during permissive hypoxemia and may be a
useful alternative to increasing FiO2 or PEEP, particularly when
relatively unsafe levels have been reached.
DO2 = 1.34 x Hb x SaO2 x Qt
According to the previous equation, oxygen delivery (DO2) can be
maintained, at least theoretically by supra-normal cardiac output (Qt) if
arterial oxygen saturation is relatively low. Inotropic agents, such as
dobutamine or milrinone can be used to increase cardiac output to supra-
normal levels with only minimal increase in oxygen consumption. Volume
expansion, with crystalloids or colloids and vasodilator agents, such as
nitroprusside and nitrates can also be used.
As previously mentioned, arterial oxygen content is determined mainly by
arterial oxygen saturation and hemoglobin concentration, as the amount of
oxygen dissolved in plasma is minimal. Arterial oxygen content is reduced
during permissive hypoxemia as a result of the low arterial oxygen
saturation. In such circumstances, hemoglobin concentration would be
particularly important in determining arterial oxygen content and oxygen
delivery. However, what might be the optimal hemoglobin concentration
during permissive hypoxemia? Hébert and his colleagues in the Canadian
Critical Care Trials Group demonstrated that a restrictive strategy of red
-cell transfusion, in which hemoglobin concentration is maintained at 7 to
9 g per deciliter, is at least as effective as and possibly superior to a
liberal transfusion strategy, in which hemoglobin concentration is
maintained at 10 to12 g per deciliter (16). However, oxygen delivery and
oxygen consumption were not calculated or measured in this trial, making
it difficult to evaluate the usefulness of restrictive transfusion
strategy in critically ill patients with hypoxemia, a clinical situation
in which arterial oxygen content and oxygen delivery are reduced. Thus, it
may not be appropriate to use a hemoglobin level of less than 7 g per
deciliter as a threshold for red-cell transfusion to patients with ARDS,
especially if there is evidence of tissue hypoxia. Maintaining hemoglobin
concentration at 9 to10 g per deciliter may therefore, be advisable during
permissive hypoxemia to avoid further reduction in arterial oxygen content
and oxygen delivery.
Clinical and biochemical assessment of tissue hypoxia is important to all
patients during permissive hypoxemia. Whole-body oxygen consumption can be
measured in ventilated patients by modern gas exchange monitors.
Alternatively, VO2 can be calculated as a function of the cardiac output
and arteriovenous oxygen content difference.
VO2 = Qt x 1.34 x Hb x (SaO2 - SvO2)
However, oxygen consumption derived from this equation is less accurate
than that measured by calorimetry (17). Global assessment of tissue
hypoxia also includes mixed venous oxygen saturation, which can be
measured either intermittently by withdrawing blood from a pulmonary
arterial line or continuously by fiberoptic pulmonary artery catheter
(18). SvO2 is probably the best single indicator of the adequacy of whole-
body oxygen transport since it represents the amount of oxygen left in
systemic venous blood after passing through the tissues (19). A decrease
in SvO2 can be caused by a decrease in cardiac output, arterial oxygen
saturation or hemoglobin concentration and/or an increase in oxygen
demand. However, a normal value of SvO2 does not rule out regional tissue
hypoxia that can result from extensive redistribution of blood flow,
especially in septic shock. Regional tissue hypoxia is often difficult to
detect by global indices of tissue hypoxia, such as SvO2 or arterial blood
lactate (20, 21). In patients with ARDS and sepsis, the same limitation of
SvO2 for the detection of regional tissue hypoxia is still present,
whether permissive hypoxemia is used or not. However, in the context of
permissive hypoxemia, it may be more appropriate to use oxygen extraction
ratio rather than SvO2 as an index of global tissue hypoxia, since the
initially low SaO2 may further reduce SvO2 without necessarily indicating
increased oxygen extraction and tissue hypoxia.
O2 ER = (SaO2 - SvO2) / SaO2
Increased production of lactate is one of the most common abnormalities in
patients with tissue hypoxia. However, lactic acidosis is not specific for
tissue hypoxia and blood lactate may increase in several clinical
situations, including sepsis, without other evidence of tissue hypoxia.
Other parameters of regional tissue hypoxia include measurement of gastric
mucosal pH and cerebral oxygen extraction ratio. The adequacy of cerebral
oxygenation can be evaluated invasively, by calculating cerebral oxygen
extraction ratio or non-invasively by infrared and near-infrared
spectroscopy (22).
Cerebral O2 ER = SaO2 - SvjO2 / SaO2
where SvjO2 is the oxygen saturation of internal jugular venous blood.
In selected patients with coronary artery disease, myocardial oxygenation
can be evaluated by measuring myocardial blood lactate, oxygen extraction
ratio and regional pH during transvenous catheterization of the coronary
sinus that drains most of the cardiac veins and opens into the right
atrium. Non-invasive assessment of myocardial oxygenation can be performed
with electrocardiography, to detect ST segment -T wave changes and
echocardiography for evaluating the left ventricular function and regional
wall motion. Renal function should also be closely monitored with urine
output, BUN and creatinine. In conclusion, permissive hypoxemia is a
hypothetical ventilatory strategy that focuses on maintaining adequate
tissue oxygenation rather than arterial oxygen saturation. During
permissive hypoxemia, relatively low SaO2 (as low as 85 or 80 percent) may
be accepted, without necessarily increasing the FiO2 or PEEP, as long as
there is no evidence of significant tissue hypoxia. Permissive hypoxemia
can therefore, reduce the incidence of pulmonary oxygen toxicity, alveolar
overdistension, multi-organ failure and death in patients with ARDS. In
addition, I may hypothesize that oxygen delivery can be maintained within
normal or near-normal value by augmenting cardiac output and minimizing
oxygen demand of the body, thereby reducing the risk of tissue hypoxia.
Finally, permissive hypoxemia remains hypothetical until evaluating its
impact on mortality and morbidity of patients with ARDS.
References
(1) Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory
distress syndrome in adults. Lancet 1967;2:319-323.
(2) Bernard GR, Artigas A, Brigham KL, et al. The American-European
Consensus Conference on ARDS: definitions, mechanisms, relative outcomes
and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818-
824.
(3) Parker JC, Hernandez LA, Peevy KJ. Mechanisms of ventilator-induced
lung injury. Crit Care Med 1993;21:131.
(4) Dreyfuss D, Saumon G. barotrauma is volutrauma, which volume is the one
responsible? [editorial]. Intensive Care Med 1992;18:139.
(5) Lachmann B. Open up the lung and keep the lung open [editorial;
comment]. Intensive Care Med 1992;18;319.
(6) Ranieri VM, Suter PM, Tortorella C, et al. Effects of mechanical
ventilation on inflammatory mediators in patients with acute respiratory
distress syndrome: a randomized controlled trial. JAMA 1999;282:54-61.
(7) Montgomry A.B.M.A, Stager CJ, Caricco and Hudson LD. Causes of
mortality in patients with the adult respiratory distress syndrome. Am Rev
Respir Dis 1985;132:485.
(8) Davis WB, Rennard SI, Bitterman PD, Crystal RG. Pulmonary oxygen
toxicity. Early reversible changes in human alveolar structures induced by
hyperoxia. N Engl J Med 1983;309:878.
(9) Witschi HR, Haschek WM, Klein-Szanto AJ, et al. Potentiation of diffuse
lung damage by oxygen. Am Rev Respir Dis 1981;123:98-103.
(10) Connie CW, Hsia MD. Respiratory Function of Hemoglobin. N Engl J
Med 1998;338:239.
(11) Guyton AC, Hall JE. Transport of Oxygen and Carbon Dioxide in the
Blood and Body Fluids. Textbook of Medical Physiology, 2000.p.463-473.
(12) Hochachka PW. Defence strategies against hypoxia and hypothermia.
Science 1986;231:234.
(13) Rob Law, Bukwirwa H. The physiology of Oxygen Delivery. Update in
Anaesthesia 1999;10:3.
(14) Steltzer H, Kraft P, Fridich P, et al. Right ventricular function and
oxygen transport patterns in patients with acute respiratory distress
syndrome. Anaesthesia 1994;49:1039.
(15) Roy G, Brower MD, Loraraine B, et al. Treatment of ARDS. Chest
2001;120:1347.
(16) He'bert PC, Wells G, Blajchman MA, et al. A multicenter,
randomized, controlled clinical trial of transfusion requirements in
critical care. N Engl J Med 1999;340:409-417.
(17) Takala J, Keinanen O, Vaisanen P, Kari A. Measurement of gas exchange
in intensive care : laboratory and clinical validation of a new device.
Crit Care Med 1989; 17:1041.
(18) Armaganidis A, Dhainaut JF, Billard JL, Klouche K, Mira JP, et al.
Accuracy assessment of three fiberoptic pulmonary artery catheters for
SvO2 monitoring. Intensive Care Med 1994;20:484.
(19) Weissman C, Kemper M. The oxygen uptake-oxygen delivery relationship
during ICU interventions. Chest 1991;99:430.
(20) Third European Consensus Conference in Intensive Care. 1996. Paris 7-8
December, 1995. Tissue hypoxia: how to detect, how to correct, how to
prevent? Reanimation Urgencies, 5, 161, 320.
(21) Ruokonen E, Takala J, Kari A, et al. Regional blood flow and oxygen
transport in septic shock. Crit Care Med 1993;21:1296.
(22) Mancini DM, Bolinger L, Li K, et al. Validation of near-infrared
spectroscopy in humans. J Appl Physiol 1994;77:2740.
In the results we can observe that the control of illness is better
in the SM group but you say also that there were a saving in inhaled
corticosteroids.... so how can you explain the best control? May be the
environmental control or there are others explanations?
The British Thoracic Society (BTS) guidelines for the management of
primary spontaneous pneumothorax (PSP) recommend simple aspiration as the
first line treatment for all cases of PSP requiring intervention.[1]
However, studies in the UK have shown that compliance is poor, and that
simple aspiration is under-utilised.[2,3] Henry et al suggested that poor
compliance may be due to an unwillingness to...
The British Thoracic Society (BTS) guidelines for the management of
primary spontaneous pneumothorax (PSP) recommend simple aspiration as the
first line treatment for all cases of PSP requiring intervention.[1]
However, studies in the UK have shown that compliance is poor, and that
simple aspiration is under-utilised.[2,3] Henry et al suggested that poor
compliance may be due to an unwillingness to aspirate.[1] Medical staff
tends to have concerns over the increased likelihood of failure of simple
aspiration for larger pneumothoraces. But are these concerns actually
justified?
We showed, in a study recently published, that larger size of
pneumothorax is significantly associated with failed aspiration.[4] We
retrospectively studied 91 consecutive cases of PSP treated by simple
aspiration. All cases were treated at the emergency department of an
university teaching hospital in Hong Kong, China, over a two-year period.
Our protocol had closely followed the BTS guidelines.[5] The overall
success rate was 50.5%. Failed cases had significantly larger sizes of
pneumothorax (p<_0.0005. furthermore="furthermore" pneumothorax="pneumothorax" size="size"/> 40% was
significantly associated with failure (p<_0.005. in="in" a="a" multivariate="multivariate" analysis="analysis" pneumothorax="pneumothorax" size="size" _="_"/>40%¡¦ compared to size ¡¥21-39%¡¦
independently predicted failure, with an odds ratio of 8.88 (95% CI, 2.49
to 31.63). The success rate for patients with pneumothorax size 40% or
larger was only 15.4%.
Based on evidence from this study, our guidelines for the management
of PSP have been revised. For patients with pneumothorax size 40% or
above, simple aspiration is no longer the first line treatment, and chest
tube drainage is the preferred modality.
References
(1) Henry M, Arnold T, Harvey J. BTS guidelines for the management
of spontaneous pneumothorax. Thorax. 2003;58(Suppl II):ii39-ii52.
(2) Soulsby T. British Thoracic Society guidelines for the
management of spontaneous pneumothorax: do we comply with them and do they
work? J Accid Emerg Med. 1998; 15(5):317-21.
(3) Mendis D, El-Shanawany T, Mathur A, et al. Management of
spontaneous pneumothorax: are British Thoracic Society guidelines being
followed? Postgrad Med J. 2002;78:80-84.
(4) Chan SSW, Lam PKW. Simple aspiration as initial treatment for
primary spontaneous pneumothorax: Results of 91 consecutive cases. J Emerg
Med. 2005;28:133-138.
(5) Chan SSW. Current opinions and practices in the treatment of
spontaneous pneumothorax. J Accid Emerg Med. 2000;17:165-169.
In their response to our article Dr Griffiths makes some important
remarks, which we would like to comment on.
We did indeed take clustering into account in the analysis of our
data. As stated in the methods section of our paper we used multilevel
models.[1] In this multilevel model practices were included as the level
of clustering in these models.
In their response to our article Dr Griffiths makes some important
remarks, which we would like to comment on.
We did indeed take clustering into account in the analysis of our
data. As stated in the methods section of our paper we used multilevel
models.[1] In this multilevel model practices were included as the level
of clustering in these models.
A second methodological question is about the successfully treated
weeks. This is indeed a new unvalidated method, which was not described in
detail in the original trial protocol. Initially only a comparison of
monthly/weekly symptom scores was planned. As the study progressed we
developed a more profound insight in how to express the day-to-day
variability of asthma symptoms, which is characteristic for the
intermittent nature of the disease. When we graphically plotted symptom
scores in time for each patient, scores were clearly skewed towards the
lower values. A pattern we have observed in several previous asthma
studies at our department. Our goal was to define an effect parameter that
would give expression to this observation in order to detect and count
episodes of perceived loss of asthma control as perceived by patients. For
most patients symptom scores were similar to the graphical representation
of symptom scores as shown in figure 1 in our paper. Our assumption was
that the peaks in this figure represent episodes of perceived loss of
asthma control. Ideally an individual (baseline) cut-off score should have
been defined before the start of the study. As this was not possible in
our study, we compared several cut-off points (individual median,
individual mode, individual median +1) with a 'blinded' manual count of
peaks in a sample of symptom score graphs. The individual median value
proved to have the best match with our counts. Possible strengths and
weaknesses of this analysis have been described in the discussion section
of our paper and we have planned further validation on other datasets at
our department.
Finally Dr Griffiths points out that benefits of self-management in
our study are at best marginal. He doubts if benefits described are worth
the efforts and resources spent. From the sole perspective of outcomes as
described in our paper it seems tempting to disqualify self-management
because of a lack of superiority. However, in a cost-effectiveness
analysis we demonstrated that self-management is at least equally
efficient as usual care. Savings in medication and productivity loss
equalled resources allocated for the implementation of self-management.
Effects in favour of self-management were more pronounced in the second
year, suggesting a long-term superiority (ie dominance in terms of cost-
effectiveness) of self management.[2] In addition patients were more
satisfied with the care provided by their GP.[3] Self-management of
asthma provides a unique opportunity for a more patient centered approach,
without compromising asthma control and without spending additional
resources.
We believe that self-management is worth the effort in spite of the
absence of clear clinical evidence of superiority. The economic benefits
of self management in terms of a reduced number of days out of work may
illustrate the need to take a broader view than just the process and
outcomes of the asthma care itself. It is in particular on these grounds
that we are confident to promote self-management.
References
(1) Thoonen BPA, Schermer TRJ, van den Boom G, Molema J, Folgering H,
Akkermans RP et al. Self-management of asthma in general practice, asthma
control and quality of life: a randomised controlled trial. Thorax
2003;58:30-6.
(2) Schermer TRJ, Thoonen BPA, van den Boom G, Akkermans RP, Grol RP,
Folgering HT et al. Randomized Controlled Economic Evaluation of Asthma
Self-Management in Primary Health Care. Am J Respir Crit Care Med
2002;155:1062–72.
(3) Thoonen BPA, Schermer TRJ, Jansen M, Smeele I, Jacobs JE, Grol R
et al. Asthma education tailored to individual patient needs can optimise
partnerships in asthma self-management. Patient Education and Counseling
2002;47:355-60.
Reactivation of tuberculosis (TB) is a major concern during treatment with
TNF inhibitors [1]. Different guidelines to detect active and latent TB
have been reccomended in various countries before starting therapy with
these drugs. There is evidence that their application has led to a
significant reduction in the number of cases of TB [2], but we do not know
which is the most cost-effective strategy.
At...
Reactivation of tuberculosis (TB) is a major concern during treatment with
TNF inhibitors [1]. Different guidelines to detect active and latent TB
have been reccomended in various countries before starting therapy with
these drugs. There is evidence that their application has led to a
significant reduction in the number of cases of TB [2], but we do not know
which is the most cost-effective strategy.
At our Department 69 consecutive patients with rheumatoid arthritis (53
pts), ankylosing spondylitis (10 pts) and psoriatic arthritis (6 pts)
considered for treatment with TNF inhibitors have been recently screened
for TB infection according to the Italian guidelines. All of them
underwent a careful history, tuberculin skin testing by injecting 0.2 ml
of 10 TU PPD intradermally (Mantoux method) and chest x-rays. In order to
enhance sensitivity of tuberculin testing we had stopped steroid treatment
in all patients at least one week before performing the test. Patients
were considered affected by latent TB if there was any of the following
conditions: 1)unequivocal history of previous TB; 2) positive tuberculin
reaction (at least 5 mm of skin induration at 72 hours); 3) radiographic
lesions consistent with old TB (calcified nodular lesions, apical
fibrosis, pleural scarring). According to our guidelines, patients with
latent TB undergoing treatment with TNF inhibitors received preventive
chemotherapy.
Our patients were predominantly women (63.8%) with a mean age of 55.8
years (range 21-81). We found history of previous TB in 2.9% of them,
tuberculin positivity in 8.7%, radiographic lesions consistent with latent
TB in 20.3%. Globally, a diagnosis of latent TB was made in 24.6% of our
patients. Six of them underwent treatment with TNF inhibitors (notably 5/6
had a negative tuberculin test). In all of them we had to start preventive
chemotherapy with isoniazide, but in 4/6 we had to stop this drug due to
the development of liver toxicity.
Our data suggest that tuberculin skin testing is not sufficiently
sensitive to detect latent TB in patients with rheumatoid arthritis and
other spondyloarthropaties, as well as in those with inflammatory bowel
diseases [3]. In these patients chest radiography is mandatory if we do
not want to miss a significant proportion of cases. The Italian guidelines
for TB screening before starting treatment with TNF inhibitors allow
recognition of these cases, increasing the indications to preventive
chemotherapy. However, liver toxicity caused by isoniazide may be enhanced
in these patients, probably due to concomitant therapy with other drugs
such as methotrexate and NSAIDs. This suggests that the risk of
chemoprophylaxis should be compared with the chance of contracting TB in
the individual patient and that a cost-effectiveness evaluation of the
different strategies used to minimize the risk of TB reactivation during
treatment with TNF inhibitors would be indicated.
References
(1) Wolfe F, Michaud K, Anderson J, Urbansky C. Tuberculosis infection
in patients with rheumatoid arthritis and the effect of infliximab
therapy. Arthritis Rheum 2004; 50: 372-9.
(2) Gomez-Reino JJ, Carmona l, Valverde VR, et al. Treatment of rheumatoid
arthritis with tumour necrosis factor inhibitors may predispose to
significant increase in tuberculosis risk. A multicenter active-
surveillance report. Arthritis Rheum 2003; 48: 2122-7.
(3) Mow WS, Abreu-Martin MT, Papadakis KA, et al. High incidence of anergy
in inflammatory bowel disease patients limits the usefulness of PPD
screening before infliximab therapy. Clin Gastroenterol Hepatol 2004; 2:
309-13.
Dear Editor
Medication compliance in asthma is disappointingly low and leads to poor asthma control in children. It is very common that parents do not supervise treatment and often report poor asthma control. Many difficult-to-manage asthmatics have ongoing exposure to allergens or other asthma triggers. In such instances, required medication may be very high and the results may be disappointing. Only 30% of pediatric a...
Dear Editor
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Dear Editor
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Dear Editor
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Dear Editor
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It is not clear whether clustering has bee...
Dear Editor
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Dear Editor
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Dear Editor
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Dear Editor
In their response to our article Dr Griffiths makes some important remarks, which we would like to comment on.
We did indeed take clustering into account in the analysis of our data. As stated in the methods section of our paper we used multilevel models.[1] In this multilevel model practices were included as the level of clustering in these models.
A second methodological questio...
Dear Editor
Reactivation of tuberculosis (TB) is a major concern during treatment with TNF inhibitors [1]. Different guidelines to detect active and latent TB have been reccomended in various countries before starting therapy with these drugs. There is evidence that their application has led to a significant reduction in the number of cases of TB [2], but we do not know which is the most cost-effective strategy. At...
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