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This article discusses non-invasive methods for monitoring haemoglobin and the impact they have in medicine, particularly in emergency room and intensive care situations
Department of Anaesthesiology and Critical Care Medicine,
Saint Louis – Lariboisière – Fernand Widal University Hospital, Paris, France
Paris Diderot University, Paris, France
Recent recommendations suggest monitoring cardiac output; however one should remember that among the determinants of oxygen transport, oxygen saturation and haemoglobin concentration play a key role. Whilst oxygen saturation can be easily monitored in real-time with oximetry, haemoglobin necessitates a blood sample and an analysis. Spectrophotometry is the reference method for measuring haemoglobin concentration from a venous blood sample. This technique takes at least 45 minutes. Over the last few years, systems allowing real-time and non-invasive haemoglobin monitoring have been developed. However, the validity of these monitors remains questionable. Studies are scarce with reserved or contradictory results when applied to haemodynamically unstable patients since low perfusion can lead to erroneous measurements using non-invasive haemoglobin monitors.
Why should we monitor haemoglobin?
A red blood cell can schematically be represented as a bag (the membrane), containing haemoglobin and enzymes. A haemoglobin molecule is made up of four subunits, with each containing a haem and globin complex. Its function is to transport oxygen from the lungs to peripheral tissues. If anaemia has an acute onset, the organism has no time to adapt to this new condition in oxygen content and causes more damage. There is no routine monitoring device that can provide information on the adequacy between tissue oxygenation and perfusion. Recent recommendations suggest to monitor cardiac output,1 but Figure 1 shows that oxygen transport, oxygen saturation and haemoglobin concentration are crucial as well.
Haemoglobin concentration assessment requires invasive monitoring procedures as well as analysis but oxygen saturation can be measured using oximetry easily in real-time. Normal haemoglobin concentration varies from 13.5–17.5g/dl in men and from 12.5–16.5g/dl in women. There are still controversies regarding transfusion thresholds. Despite numerous studies, there is no consensus on transfusion thresholds in the case of haemorrhage.
Although transfusion strategies include the patient’s comorbidities, context, onset timing and clinical signs of poor tolerance, it is still mainly based on the haemoglobin value. In 2006, the American Society of Anaesthesiology published recommendations2 with a strong agreement for red blood cell transfusion below 6g/dl and no transfusion above 10g/dl.
In France, the 2002 ASSAPS (Agence française de sécurité sanitaire des produits de santé) recommendations3 suggest thresholds of 7g/dl for patients with no comorbidity, 8–9g/dl for patients with a history of cardiovascular disease or with sepsis and 10g/dl for patients with unstable ischaemic heart disease. These thresholds are challenged by studies in favour of restrictive strategies which do not increase mortality or cardiovascular events.4 However delayed transfusion increases morbidity and mortality.5 Whether one chooses a restrictive or liberal transfusion strategy, haemoglobin concentration is an essential to guide transfusion.
How to monitor haemoglobin non-invasively
The reference method for measuring haemoglobin concentration from a blood sample requires the use of spectrophotometry. This technique is performed in the haematology laboratory, needs withdrawal of a blood sample and takes at least 45 minutes. During acute haemorrhage, such a delay causes late diagnosis of anaemia thus slowing the patient’s care.
Real-time and bedside measurement systems exist, the most frequently used in clinical practice works by the modified azide-methaemoglobin reaction. Among the portable systems using this technique, the most commonly used is HemoCue®. It rapidly provides the haemoglobin concentration from capillary blood and does not need calibration. The use of this technique in the operating room (OR) provides reliable results when compared to the reference method,6 especially when the analysis is repeated two to three times from the same sample. However, this monitoring technique might be insufficient for patients with low capillary perfusion (vasopressor use, shock).7 Some studies indicate uneven results in surgical intensive care units (ICU).8 Furthermore, this technique does not allow continuous monitoring and needs a blood sample.
For the last few years, systems allowing real-time and non-invasive haemoglobin monitoring have been developed. The first monitor on the market was RADICAL-7 from Masimo®. It uses infrared pulse oximetry with a finger sensor analysing the pulsed wave. Using eight different wavelengths, it can distinguish different forms of bound haemoglobin and provide the total haemoglobin value.
More recently, Orsense® placed a continuous non-invasive haemoglobin monitor called NBM-200MP on the market. This low perfusion oximeter uses occlusion spectroscopy. It combines infrared spectrophotometry optical measurements with temporary blood flow occlusion using a pneumatic cuff. The occlusion induces a signal allowing fine haemoglobin measurements and low perfusion oximetry.
The validity of these monitors remains questionable. Even though many studies were published since their placement on the market, patients included were stable,9,10 so therefore it is not relevant for acute haemorrhage in the OR or unstable ICU patients with vasopressors.
Results from studies (of which there are not many) tend to be contradictory with regards to haemodynamically unstable patients. This is because low perfusion can result in erroneous measurements when non-invasive haemoglobin monitors are used. Results in critically ill patients, apart from haemorrhagic shock, are satisfactory.11 However, when studying patients with low haemoglobin and/or haemorrhagic shock, values can vary from 1g/dl12 to 1.5g/dl.13,14 Likewise, Gayat et al.15 studied patients admitted to the emergency room and found a 1.8g/dl bias. Such a lack of precision implies confirmation of the haemoglobin value using HemoCue® or a laboratory sample analysis. Nonetheless, companies producing these monitors regularly update their algorithm to minimise measurement biases. Kim et al.recently published a meta-analysis in 2014,16 including 32 studies from 2005 to 2013 and compared haemoglobin measurements using non-invasive monitors to results from haematology laboratory. Among the 4425 patients included, the mean bias was 0.10 ±1.37g/dl with agreement limits of –2.59 to 2.80g/dl. Subgroup analysis found a 0.39 bias ±1.32g/dl with an agreement limit of –2.21 to 2.98g/dl concerning 13 studies in the perioperative context and –0.51 bias ±1.59g/dl with agreement limits of –3.63 to 2.62g/dl concerning five studies in ICU. Therefore the conclusion is that differences between the two measurement methods were small, however practitioners should be careful when making decisions solely on these monitors.
Non-invasive haemoglobin monitoring is a great medical breakthrough. In the OR, emergency room and ICU, haemoglobin measurements are performed very regularly. Yet the reference laboratory method using blood samples seems greatly able to improve in terms of invasiveness, cost and time consumption. Each measurement needs someone for sampling, waking up the patient, inducing pain, and this takes a minimum of 45 minutes. Non-invasive haemoglobin monitors appear attractive for all these reasons. Nevertheless, most of them lack precision particularly for patients who would benefit the most from a non-invasive continuous real-time monitoring: patients in haemorrhagic shock, unstable patients or acutely anaemic patients. This is a major limit for their use in the OR, emergency room and ICU. To this day it seems unreasonable to solely base a transfusion strategy on non-invasive methods without blood sample analysis as a confirmation. In the future, monitor improvements will allow sufficient precision, even though there is still a long way to go.