It is difficult or impossible to achieve adequate blinding in trials designed to compare resuscitation strategies. To overcome the potential for bias introduced by the absence of blinding, investigators have stressed the importance of using protocolized care for both the intervention and control arms. In the trial conducted by Rivers and coworkers 1, control individuals were resuscitated using an algorithm that included the administration of fluid boluses titrated to increase central venous pressure (CVP) to 8–12 mmHg. Vasopressors were titrated to maintain mean arterial pressure between 65 and 90 mmHg. Maintaining urine output at 0.5 ml/kg per hour or greater was also a stated resuscitation target, although the strategies to be used to achieve this goal were not specified. Of individuals in the control group, 86% achieved these hemodynamic and urine output targets, whereas 99% of those in the intervention group achieved hemodynamic and SCVO₂ goals 1.

Data obtained in a large multicentric RCT support the view that a liberal red cell transfusion policy designed to maintain hemoglobin concentration at 10 g/dl or greater may be deleterious in stable, critically ill patients 15. However, the effects of red blood cell transfusion during the resuscitation of acutely ill, septic patients may be different. Both Hayes 12 and Gattinoni 13 and coworkers used the same threshold for transfusion (hemoglobin concentration <10 g/dl) as was used by Rivers and colleagues 1.

A recent meta-analysis 16 suggested that aggressive resuscitation efforts that begin early (before the onset of organ failure) may prove more beneficial than resuscitation carried out after the establishment of organ failure. Gattinoni and coworkers 13 enrolled patients in the SVO₂ trial after 48 hours in the ICU, and Hayes and colleagues 12 enrolled patients upon arrival at the ICU, irrespective of the time from the presumed onset of critical illness. Thus, both of these (negative) studies enrolled patients who were already in an ICU. In contrast, Rivers and colleagues 1 enrolled patients on presentation to the emergency department. These patients had already received 6 hours of protocolized care before their arrival in the ICU. Thus, early identification and initiation of treatment may be a key element in the effectiveness of resuscitation interventions. Perhaps by actively enrolling individuals with cryptic sepsis or compensated shock, Rivers and colleagues intervened at a point before multisystem organ dysfunction had developed.

Rivers and coworkers 1 enrolled only patients with a suspected infection presenting to the emergency department with two out of four SIRS criteria and hypotension after a fluid bolus or an elevated blood lactate concentration. Thus, the study focused on patients with clear evidence of tissue hypoperfusion. In contrast, both the Hayes 12 and Gattinoni 13 studies enrolled a diverse population of critically ill patients at varying times throughout their illness.

In the intervention (experimental) arms of both the Hayes 12 and Gattinoni 13 trials, the goals for resuscitation were indices (cardiac index and systemic oxygen delivery) that are usually measured using a pulmonary artery catheter (PAC). In contrast, the end-point for resuscitation in the trial by Rivers and coworkers 1 was a parameter (SCVO₂) that was measured by using an oximetric central venous catheter. Is it possible that the positive results in the study by Rivers and colleagues were simply due to the difference in the primary end-point for resuscitation? Although it is hard to be certain, this notion seems improbable to us. Recall that the trial performed by Gattinoni and coworkers 13 included a third arm in which patients were resuscitated to a SVO₂ of greater than 70% (measured using a PAC). The patients in this arm of the study did not fair any better than those in the other two arms.

Physical examination and vital signs have traditionally been used to screen for hypovolemia and/or shock. However, heart rate, blood pressure, and capillary refill are not sensitive predictors of hypovolemia 19. Moreover, these 'vital signs' do not correlate with other indicators of shock that require more invasive methods for measurement. In one study 20, 50% of critically ill patients presenting with shock and resuscitated to normal vital signs continued to have elevated blood lactate levels and low SCVO₂.

Recently, there has been considerable interest in pulse pressure or systolic pressure variation as clinical predictors of preload responsiveness, but these signs predict the response to fluid loading – not whether fluid is likely to beneficial 21. Nevertheless, it seems reasonable to hypothesize that optimizing preload will improve outcome, particularly if the strategy is instituted early in the course of illness (e.g. during the first 6 hours after presentation). Normalization of blood lactate level or base deficit might also be of value, but continuous monitoring of blood pH or lactate concentration is not currently available in most centers.

Circulating levels of procalcitonin 22, TREM-1 23, molecules associated with induction of apoptosis (e.g. tumor necrosis factor and Fas ligand) 24, interleukin-6 25, and other biochemical indices of inflammation have been proposed as diagnostic markers of sepsis and SIRS. These markers may be clinically useful in the initial diagnosis and stratification of sepsis 26, but these parameters are not useful for the minute-to-minute titration of care.

It is well established that a high blood lactate concentration portends a poor prognosis for patients with shock due to various causes 272829303132. Furthermore, a prompt decrease in circulating lactate level in response to resuscitation is a good prognostic indicator 33. These considerations notwithstanding, measurements of blood lactate concentration are not useful for the titration of resuscitation because this biochemical parameter responds too slowly to changes in perfusion and, by itself, blood lactate concentration provides no information regarding key parameters such as preload responsiveness.

The goal of resuscitation is to ensure adequate oxygen delivery to tissues. At the level of the whole body, oxygen delivery is the product of cardiac output and arterial oxygen content. In septic shock, the predominant reason for low cardiac output is inadequate preload. CVP is often used as a surrogate for preload 34. However, even direct measurements of left atrial pressure do not correlate perfectly with left ventricular end-diastolic volume (i.e. preload), because the relationship between intracavitary volume and pressure is inconsistent both among patients and in the same patient over time 3536. CVP, of course, is even less likely than left atrial pressure to reflect left ventricular end-diastolic volume accurately, because it is affected by right ventricular afterload (i.e. pulmonary arterial pressure) as well as right ventricular compliance.

For many years, the PAC was considered the 'gold standard' for monitoring systemic hemodynamic parameters, such as cardiac output, left ventricular preload, and systemic oxygen delivery. The PAC can be used to measure central venous and pulmonary artery pressures. Using thermodilution, this device permits repetitive or even continuous estimates of cardiac output. In addition, whether by using oximetric technology or blood gas analysis, the PAC permits measurements of systemic oxygen delivery, SVO₂, and systemic oxygen extraction ratio.

In 1996, Connors and coworkers 37 reported surprising results in a major observational study evaluating the value of pulmonary artery catheterization in critically ill patients. Those investigators took advantage of an enormous data set that had previously been (and prospectively) collected for another purpose at five major teaching hospitals in the USA. They compared two groups of patients: those who did and those who did not undergo placement of a PAC during their first 24 hours of ICU care. They recognized that the value of their intended analysis was completely dependent on the robustness of their methodology for case matching, because sicker patients (i.e. those at greater risk for mortality based on the severity of their illness) were presumably more likely to undergo pulmonary artery catheterization. Accordingly, the authors used sophisticated statistical methods for generating a cohort of study (i.e. PAC) patients, each one having a paired control matched carefully for severity of illness. A critical assessment of their published findings supports the view that the cases and their controls were indeed well matched with respect to a large number of pertinent clinical parameters. Remarkably, Connors and coworkers concluded that placement of a PAC during the first 24 hours of stay in an ICU is associated with a significant increase in the risk for mortality, even when statistical methods are used to account for severity of illness.

Although the report by Connors and coworkers 37 generated an enormous amount of controversy in the medical community, the results reported actually confirmed the results of two prior similar observational studies. The first of these studies 38 used a database of 3263 patients with acute myocardial infarction treated in central Massachusetts in 1975, 1978, 1981, and 1984 as part of the Worcester Heart Attack Study. For all patients, hospital mortality was significantly greater for patients treated using a PAC, even when multivariate statistical methods were employed to control for key potential confounding factors. The second large observational study of patients with acute myocardial infarction 39 also found that hospital mortality was significantly greater for patients managed with the assistance of a PAC, even when the presence or absence of 'pump failure' was considered in the statistical analysis. In neither of these earlier reports did the authors conclude that placement of a PAC was truly the cause of worsened survival after myocardial infarction. As a result of the study by Connors and coworkers, experts in the field questioned the value of bedside pulmonary artery catheterization, and some even called for a moratorium on the use of the PAC 40.

Since publication of the 'Connors study' 37, a large observational study of patients admitted to a medical ICU 41 concluded that patients who underwent placement of a PAC were sicker than those who did not receive this type of monitoring. However, risk-adjusted mortality was similar for patients treated with and those treated without use of a PAC.

Relatively few prospective RCTs of pulmonary artery catheterization have been performed. All of these studies are flawed in one or more ways. The study by Pearson and coworkers 42 was very underpowered; only 226 patients were enrolled. In addition, the attending anesthesiologists were permitted to exclude patients from the CVP group at their discretion; thus, randomization was compromised. The study by Tuman and coworkers 43 was large (1094 patients were enrolled), but different anesthesiologists were assigned to the different groups. Furthermore, 39 patients in the CVP group underwent placement of PAC because of hemodynamic complications. All of the individual single-institution studies of vascular surgery patients were relatively underpowered 44454647, and all excluded at least certain categories of patients (e.g. those with a history of recent myocardial infarction).

In the largest RCT to evaluate the use of the PAC, Sandham and coworkers 48 randomly assigned 1994 high-risk patients undergoing major thoracic, abdominal, or orthopedic surgery to placement of a PAC or a CVP catheter. In the patients assigned to receive a PAC, physiologic goal-directed therapy was implemented by protocol. There were no differences at 30 days, 6 months, or 12 months in mortality between the two groups, and ICU length of stay was similar. There was a significantly higher rate of pulmonary emboli in the PAC group (0.9% versus 0%). This study has been criticized because most of the patients enrolled were not in the highest risk category.

The limitations of these studies notwithstanding, the weight of current evidence suggests that routine use of the PAC is not useful for the vast majority of patients undergoing cardiac, major peripheral vascular, or ablative surgical procedures. Whether use of a PAC for early goal-directed resuscitation of patients with sepsis would lead to results better or worse than those obtained by Rivers and coworkers 1 is not known. It is clear, however, that if routine placement of a central venous catheter would stress the capabilities of most emergency departments, then routine PAC placement would be even more problematic.

When ultrasonic sound waves are reflected by moving erythrocytes in the bloodstream, the frequency of the reflected signal is increased or decreased, depending on whether the cells are moving toward or away from the ultrasound source. This change in frequency is called the Doppler shift, and its magnitude is determined by the velocity of the moving red blood cells. Thus, measurements of Doppler shift can be used to calculate red blood cell velocity. With knowledge of both the cross-sectional area of a vessel and the mean red blood cell velocity of the blood flowing through it, one can calculate blood flow rate. If the vessel in question is the aorta, then cardiac output can be calculated.

Two approaches have been developed for using Doppler ultrasonography to estimate cardiac output. The first approach uses an ultrasonic transducer, which is manually positioned in the suprasternal notch and focused on the root of the aorta. Aortic cross-sectional area can be estimated using a nomogram (that factors in age, height, and weight), back calculated if an independent measure of cardiac output is available, or by using two-dimensional transthoracic or transesophageal ultrasonography. Although this approach is completely noninvasive, it requires a highly skilled operator in order to obtain meaningful results and is quite labor intensive. Moreover, unless cardiac output measured using thermodilution is used to back calculate aortic diameter, accuracy using the suprasternal notch approach is not acceptable 4950. Accordingly, the method is useful only for obtaining very intermittent estimates of cardiac output and has not been widely adopted by clinicians.

Another more promising approach was originally introduced by Daigle and colleagues 51. In this method, blood flow velocity is continuously monitored in the descending thoracic aorta using a transducer introduced into the esophagus. The current embodiment of this concept, called the CardioQ, is manufactured by Deltex Medical Limited (Chichester, UK). The device consists of a continuous wave Doppler transducer mounted at the tip of a transesophageal probe. In order to maximize the accuracy of the device, the probe position must be adjusted to obtain the peak velocity in the aorta. To transform blood flow in the descending aorta into cardiac output, a correction factor is applied, which is based on the assumption that only a portion of the flow at the root of the aorta is still present in the descending thoracic aorta. Aortic cross-sectional area is estimated using a nomogram based on the patient's age, weight, and height. Results using these methods appeared to be sufficiently accurate across a broad spectrum of patients to be clinically useful 52. In that multicenter study, good correlation was found between cardiac output measurements obtained using the esophageal Doppler method and thermodilution. The ultrasound device also calculates a derived parameter, called flow time corrected (FTc), which is the systolic flow time in the descending aorta corrected for heart rate. FTc is a function of preload, contractility, and vascular input impedance. Although it is not a pure measure of preload, Doppler-based estimates of stroke volume and FTc have been used successfully to guide volume resuscitation in high-risk surgical patients undergoing major operations 53. Indeed, evidence is accumulating that esophageal Doppler monitoring coupled with algorithmic resuscitation improves outcomes in surgical patients 5455.

The impedance to flow of alternating electrical current in regions of the body is commonly called 'bioimpedance'. In the thorax, changes in the volume and velocity of blood in the thoracic aorta lead to detectable changes in bioimpedance. The first derivative of the oscillating component of thoracic bioimpedance (dZ/dt) is linearly related to aortic blood flow. On the basis of this relationship, empirically derived formulas have been developed to estimate stroke volume (and hence cardiac output) noninvasively. This methodology is called impedance cardiography. The approach is attractive because it is completely noninvasive, provides a continuous read-out of cardiac output, and does not require extensive training for use. Despite these advantages, a number of studies suggest that measurements of cardiac output obtained by impedance cardiography are not sufficiently reliable to be used for clinical decision making and have poor correlation with standard methods such as thermodilution and ventricular angiography 565758.

Perhaps one of the least invasive and most appealing methods for determining cardiac output uses an approach called pulse contour analysis, originally described by Wesseling and colleagues 59 for estimating stroke volume on a beat-to-beat basis. The mechanical properties of the arterial tree and stroke volume determine the shape of the arterial pulse waveform. The pulse contour method of estimating cardiac output uses the arterial pressure waveform as an input in a model of the systemic circulation in order to determine beat-to-beat stroke volume. The parameters of resistance, compliance, and impedance are initially estimated based on the patient's age and sex, and can be subsequently refined by using a reference standard measurement of cardiac output. A commercially available device, the PulseCO Hemodynamic Monitor (LiDCO, Ltd, London, UK) utilizes this technology. In the LiDCO system, the reference standard estimation of cardiac output is obtained periodically using the indicator dilution approach by injecting the indicator (a dilute solution of lithium ion) into a central venous catheter and detecting the transient increase in lithium ion concentration in the blood using an arterial catheter equipped with a lithium-sensitive sensor in a femoral artery.

Measurements of cardiac output based on pulse contour monitoring are comparable in accuracy to standard PAC thermodilution methods, but they use an approach that is much less invasive because arterial and central venous, but not transcardiac, catheterization is needed 60. Using online pressure waveform analysis, the computerized algorithms can calculate stroke volume, cardiac output, systemic vascular resistance, and an estimate of myocardial contractility, namely the rate of rise in arterial systolic pressure (dP/dT). One weakness of the pulse contour approach is that it does not directly provide an assessment of preload responsiveness. However, this information can be obtained by analyzing changes in pulse pressure over the respiratory cycle in mechanically ventilated patients (see below).

The use of pulse contour analysis has been applied using an even less invasive technology based on totally noninvasive photoplethysmographic measurements of arterial pressure 61. However, the accuracy of this technique has been questioned 62 and its clinical utility remains to be determined.

Partial carbon dioxide rebreathing uses the Fick principle to estimate cardiac output noninvasively. By intermittently altering the dead space within the ventilator circuit via a rebreathing valve, changes in carbon dioxide production (VCO₂) and end-tidal carbon dioxide (ETCO₂) are used to determine cardiac output using a modified Fick equation (cardiac output = VΔCO₂/ΔETCO₂) 63. A commercially available device, the NICO monitor (Novametrix Medical Systems, Inc., Wallingford, CT, USA) uses this Fick principle to calculate cardiac output using intermittent partial carbon dioxide rebreathing through a disposable rebreathing loop. The device consists of a carbon dioxide sensor based on infrared light absorption, an airflow sensor, and a pulse oximeter. Changes in intrapulmonary shunt and hemodynamic instability impair the accuracy of cardiac output estimated by partial carbon dioxide rebreathing. Continuous in-line pulse oximetry and fractional inspired oxygen are used to estimate shunt fraction to correct the cardiac output value obtained.

Some studies of the partial carbon dioxide rebreathing approach suggest that the accuracy of the NICO system is not good when thermodilution is used as the gold standard for measuring cardiac output 6465. However, other studies suggest that the partial carbon dioxide rebreathing method for determination of cardiac output compares favorably with measurements made using a PAC in critically ill patients 66. Like some of the other minimally invasive methods discussed above, the NICO system does not provide a direct assessment of preload responsiveness.

Transesophageal echocardiography (TEE) has made the transition from operating room to the ICU. TEE requires that the patient be sedated. Using this powerful technology, global assessments of left and right ventricular function can be conducted, including determinations of ventricular volume, ejection fraction, and cardiac output. Segmental wall motion abnormalities, pericardial effusions, and tamponade can readily be identified with TEE. Doppler techniques allow estimation of atrial filling pressures. The technique is somewhat cumbersome and requires considerable training and skill in order to obtain reliable results.

When intrathoracic pressure increases during the application of positive airway pressure in mechanically ventilated patients, venous return decreases and, as a consequence, stroke volume also decreases. Therefore, pulse pressure variation (PPV) during a positive pressure breath can be used to predict the responsiveness of cardiac output to changes in preload 67. PPV is defined as the difference between the maximal pulse pressure and the minimum pulse pressure divided by the average of these two pressures 67. Michard and colleagues 67 validated this approach by comparing PPV, CVP, pulmonary artery occlusion pressure, and systolic pressure variation as predictors of preload responsiveness in a cohort of critically ill patients. They classified patients as being preload responsive if their cardiac index increased by at least 15% after rapid infusion of a standard volume of intravenous fluid. Receiver operating characteristic curves demonstrated that PPV was the best predictor of preload responsiveness. Although atrial arrhythmias can interfere with the usefulness of this technique 21, PPV remains a very useful approach for assessing preload responsiveness in most patients because of its simplicity and reliability.

Global indices of cardiac output or systemic oxygen delivery provide little useful information regarding the adequacy of cellular oxygenation and mitochondrial function. On theoretical grounds, measuring tissue pH to assess the adequacy of perfusion is an extremely attractive concept. As a consequence of the stoichiometry of the reactions responsible for the substrate level phosphorylation of ADP to form ATP, anaerobiosis is inevitably associated with the net accumulation of protons 68. Accordingly, knowing that tissue pH is not in the acid range should be enough information to conclude that global perfusion (and, for that matter, arterial oxygen content) are sufficient to meet the metabolic demands of the cells, even without knowledge of the actual values for tissue blood flow or oxygen delivery. By the same token, the detection of tissue acidosis should alert the clinician to the possibility that perfusion is inadequate. Prompted by this reasoning, Fiddian-Green and colleagues 656970 promulgated the idea that tonometric measurements of tissue partial carbon dioxide tension (PCO₂) in the stomach or sigmoid colon could be used to estimate mucosal pH ('pH_i') and thereby monitor visceral perfusion in critically ill patients.

Unfortunately, the notion of using tonometric estimates of gastrointestinal mucosal pH for monitoring perfusion is predicated on a number of assumptions, some of which may be partially or completely invalid. Furthermore, currently available methods for performing measurements of gastric mucosal PCO₂ in the clinical setting remain rather cumbersome and expensive. Perhaps for these reasons, gastric tonometry for monitoring critically ill patients has never really caught on except as a research tool. Some recent developments in the field may be changing this situation, however, and monitoring tissue PCO₂ may become a practical means for assessing the adequacy of perfusion.

Although PCO₂ and pH are affected by changes in perfusion in all tissues, efforts to monitor these parameters in patients using tonometric methods have focused on the mucosa of the gastrointestinal tract, particularly the stomach, for both practical and theoretical reasons. From a practical standpoint, the stomach is already commonly intubated in clinical practice for purposes of decompression and drainage or feeding. Placement of a nasogastric or orogastric tube is generally regarded as minimally invasive. In addition, when global perfusion is compromised, blood flow to the splanchnic viscera decreases to a greater extent than does perfusion to the body as a whole 71. Thus, a marker of compromised splanchnic perfusion should be a 'leading indicator' of impending adverse changes in blood flow to other organs 72. Second, the gut has been hypothesized to be the 'motor' of the multiple organ system dysfunction syndrome 73, and in experimental models intestinal mucosal acidosis, whether due to inadequate perfusion or other causes, has been associated with hyperpermeability to hydrophilic solutes 7475. Therefore, ensuring adequate splanchnic perfusion might be expected to minimize derangements in gut barrier function and, on this basis, improve outcome for patients.

The stomach, however, may not be an ideal location for monitoring tissue PCO₂. First, carbon dioxide can be formed in the lumen of the stomach when hydrogen ions secreted by parietal cells in the mucosa titrate luminal bicarbonate anions, which are present either as a result of backwash of duodenal secretions or secretion by gastric mucosal cells. Thus, measurements of gastric PCO₂ and pH_i can be confounded by gastric acid secretion, as documented in a study of normal volunteers by Heard and coworkers 76 and subsequently confirmed by others 777879. Consequently, accurate measurements of gastric PCO₂ and pH_i depend on pharmacologic blockade of luminal proton secretion using histamine receptor antagonists or proton pump inhibitors. The need to use pharmacologic therapy adds to the cost and complexity of the monitoring strategy. Second, enteral feeding can interfere with measurements of gastric mucosal PCO₂, necessitating temporary cessation of the administration of nutritional support or the placement of a postpyloric tube 80.

Despite the problems noted above, measurements of gastric pH_i and/or mucosal–arterial PCO₂ gap have been shown to be good predictors of outcome in a wide variety of critically ill individuals, including general medical ICU patients 8182, victims of multiple trauma 838485, patients with sepsis 86, and patients undergoing major surgical procedures 7087. In studies using endoscopic measurements of gastric mucosal blood flow by laser Doppler flowmetry, the development of gastric mucosal acidosis has been shown to correlate with mucosal hypoperfusion 88. The development of low pH_i in the colon has been shown to correlate with an exaggerated host inflammatory response in patients undergoing aortic surgery 73. Moreover, in a landmark prospective multicentric RCT of monitoring in medical ICU patients, titrating resuscitation to a gastric pH_i end-point rather than conventional hemodynamic indices resulted in higher 30-day survival 89. In another study, Ivatury and coworkers 90 randomly assigned 57 trauma patients to two groups. In the first group, administration of fluids and vasoactive drugs was titrated to achieve a gastric pH_i greater than 7.30. In the second group, resuscitation was titrated to achieve a calculated systemic oxygen delivery index greater than 600 ml/min per m² or systemic oxygen utilization greater than 150 ml/min per m². Although survival was not significantly different in the two arms of the study, failure to normalize gastric pH_i within 24 hours was associated with a very high mortality rate (54%), whereas normalization of pH_i was associated with a significantly lower mortality rate (7%).

It seems likely that monitoring tissue PCO₂ ('tissue capnometry') will play an increasingly important role in the management of critically ill patients because of two important insights. First, the directly measured parameter, namely tissue PCO₂, provides more reliable information about perfusion than does the derived parameter pH_i 919293. By eliminating the potentially confounding effects of systemic hypocapnia or hypercapnia, monitoring the gap between tissue PCO₂ and arterial carbon dioxide tension (PaCO₂) may prove to be even more valuable than simply following changes in tissue PCO₂. The second recent insight is that it may not be necessary, or even desirable, to monitor tissue PCO₂ in the stomach or other portions of gastrointestinal tract. For example, Sato and coworkers 94 showed that changes in gastric wall and esophageal tissue PCO₂ track each other very closely in rats subjected to hemorrhagic shock. Similar results were reported by Guzman and coworkers 95 in a study of dogs infused with lipopolysaccharide. It appears probable that monitoring tissue PCO₂ in other nongastric sites, such as the space under the tongue, may require even less invasion of the patient and yet be as informative as measuring PCO₂ in the wall of the esophagus or the gut 9697.

Results from preliminary clinical studies support the view that monitoring tissue PCO₂ in the sublingual mucosa may provide valuable clinical information. Increased sublingual carbon dioxide tension (PslCO₂) was associated with a decrease in arterial blood pressure and cardiac output in patients with shock due to hemorrhage or sepsis 98. In a study of critically ill patients with septic or cardiogenic shock, the PslCO₂–PaCO₂ gradient was found to be a good prognostic indicator 99. This study also demonstrated that sublingual capnography was superior to gastric tonometry in predicting patient survival. The PslCO₂–PaCO₂ gradient also correlated with the mixed venous–arterial PCO₂ gradient, but it failed to correlate with blood lactate level, SVO₂, or systemic oxygen delivery. These latter findings suggest that the PslCO₂–PaCO₂ gradient may be a better marker of tissue dysoxia than are these other parameters. Similar findings were reported in another study conducted by Marik and Bankov 100. A device for sublingual capnometry, the CapnoProbe (Tyco Healthcare/Nellcor, Pleasonton, CA, USA), was being marketed commercially. The device was voluntarily recalled by the manufacturer in 2004, however, following hospital reports showing that Burkholderia cepacia, a pathogenic bacterium, could be cultured both from samples from patients monitored with CapnoProbes and from unused CapnoProbe sensors. A variety of other potentially pathogenic bacteria species were cultured from unused CapnoProbe sensors.