on 13-Sep-2021 (Mon)

Sufficient organ perfusion essentially depends on preserved macro- and micro-circulation. The last two decades brought substantial progress in the development of less and non-invasive monitoring of macro-hemodynamics. However, several recent studies suggest a frequent incoherence of macro- and micro-circulation

Regarding global micro-circulation the last two decades brought advances in a more systematic approach of clinical examination including capillary refill time, a graded assessment of mottling of the skin and accura te measurement of body surface temperatures

The main determinants of macro-circulation are pressure and flow. Both can be measured directly with a variety of techniques. Both flow and pressure are obviously connected in analogy to Ohm’s law of electric ity

Under physiological conditions, macro- and micro-circulation are inter-dependent to a high degree. By contrast, for pathological conditions such as sepsis and other etiologies of shock, the loss of this “coherence” is almost pathognomonic ( 1, 2). Under these conditions, macro- and micro-circulation are additionally modulated by interactions of inflammation and heterogenic obstruction of the micro-circulation (3)

Among the bridges from macro- to micro-circulation plasma lactate is the parameter which is most “down-stream,” i.e., close to microcirculation and cellular metabolism ( 14). A variety of experimental and clinical studies demonstrated that lactate levels indicating anaerobic metabolism increase in parallel with a decreasing ratio of oxygen utiliz ation divided by oxygen demand. Increasing lactate levels are associated with abnormal oxidative phosphorylation ( 4)

At least two trials associated decreasing lactate levels and lactate-guided early-goal directed therapy wit h improved outcome (9, 16). Finally, lact at e has become part of the new definition of septic shock (5). Based on these findings several recent guidelines recommend lactate measurement every 2 h within the first 8 h and every 8–12 h thereafter after admission with shock ( 4)

However, it has to be k ept in mind that hypoperfusion is not the only reason cause of elevated lactate levels. Impaired liver function and stress can also contribute to increases in lactate levels.

Among the parameters used as a bridge to micro-circulation, cv-a-pCO 2 -gap plays an intermediate role between S cv O 2 and lactate. Similar to S cv O 2 the veno-arterial difference in pCO 2 facilitates interpretation of adequacy of CO and resuscitation. If O 2 -extraction is impaired due to micro-circulatory mal-distribution, S cv O 2 may be normal despite a reduced CO. In this case, a c v-a-pCO 2 -gap >6 mmHg suggests inadequate perfusion, even if S cv O 2 is above 70% ( 11, 13)

Micro-circulation cannot be defined in a clear-cut formula such as Ohm’s law. Consequently, assessment of micro- circulation is more complicated due to its dependency on macro-circulation, organ-specific auto-regulatory mechanisms and interactions between certain organs

The most “accessible” organ without any instrumental approach is the sk in. Among all organs, skin has the largest weight and contributes about 16% of the body weight, i.e., about 10 kg in a normal weight adult. A structured assessment of the microcirculation of the skin starts with inspection and palpation aiming at estimation of the surface temperature. In patients with shock this allows for primary classification of “cold” shock and “warm” shock

“Warm shock” is caused by several etiologies of distributive shock including septic, anaphylactic and neurogenic shock.

The etiology of “cold shock” can be hypovolaemic, cardiogenic, or obstructive (pulmonary embolism, pericardial tamponade, pneumo-thorax)

“Warm shock” is caused by endogenous or exogenous vasodilators. Most frequently it is due to sepsis. Cold shock typically is mediated by endogenous vasoconstrictors such as nor-adrenaline which is considered as a physiological compensatory mechanism in order to provide and stabilize the perfusion of the most vit a l organs such as brain, heart and lungs. Most of the other organs including the skin are summarized as “shock organs” that can tolerate markedly reduced per fusion for a certain time

Regarding the extent of the organ skin, its impaired perfusion is not a re gional cosmetic side effect, but has systemic implications for the organism’s thermal balance. Abnormal dermal vasoconstriction or vasodilatation results in reduced or increased thermal transfer from the body core to the surface and consecutive changes in the skin temperature ( 22). Due to the absence of auto-regulatory mechanisms found in the brain, heart and lungs, skin perfusion, and temperature closely reflect the activation of neuro-humoral mechanisms during different forms of shock

The clinical assessment of the skin temperature should be performed with the investigator’s back of the hand, since this part of the hand is most sensit ive for temperature. Due to the moderate discriminatory power of this approach, a classification of the temperature as cold, sligh tly reduced, normal, and warm has been suggested.

To improve the assessment of skin temperature, two approaches can be used: 1) Instrumental measurement of skin temperature 2) Skin-core temperature gradients (SCTG)

Henning and colleagues demonstrated in 71 patients with acute circulatory failure due to myocardial infarction, sepsis or hypovolaemia that the toe ambient temperature gradient better predicted mortality than cardiac index or arterial pressure ( 25).

A study by Vincent et al. demonstrated that the association of toe-ambient temperature gradient to cardiac output was more pronounced in patients with cardiogenic shock compared to septic shock (26).

A more recent study investigating the prognostic value of the subjective assessment of peripheral perfusion in critically ill patients showed that central to toe temperature and the skin temperature gradient between the forearm and the index finger were significantly different for patients with and without abnormal peripheral perfusion which was substantially associated to outcome ( 27).

Another recent study demonstrated that toe-to-room and central-to-toe temperature gradients correlated with tissue perfusion and predicted death of multi- organ-failure in septic patients (28).

Mottling of the skin has been defined as a patchy skin discoloration that frequently starts around the knees. It is caused by heterogenic constriction of micro-vessels ( 19). More recently, a structured assessment including a staging (see Table 3) depending on the extent of mottling has been introduced by Ait- Oufella et al. ( 19). Depending on the extent of the mottled area, this score ranges from 0 to 5. High inte r-observer agreement with a kappa-value of 0.87 has been reported in this study

The use of the mottling score has been validated in several studies in patients with sepsis (32, 33) as well as liver cirrhosis (34)

In non-selected critically ill adult patients a CRT >4.5 s was associated with worse outcome. In another study a CRT >5 s was associated with perioperative complications and death after major abdominal surgery (38).

Despite the appealing simplicity of CRT there are several limitations of this parameter: The inter-observer variability has been poorly investigated and resulted in contradictory fi ndings (38–40). Furt hermore, a variety of different cut-offs are suggested depending on age and gender of the patients (39, 41, 42)

A recent study demonstrated an association of visceral organ vascular tone with CRT and mottling s c ore, but not with body surface temperature. However, skin temperature was determined in a dichotomous way (warm or cold) by subjective assessment of the examiner, but not with a thermometer or a probe ( 43).

Normalization of the skin perfusion might be used as a goal for resuscitation, since it occurs earlier during resuscitation than normalization of lactate levels (22, 37, 41).

Finally, a structured combination of clinical parameters of the skin perfusion might improve resuscitation compared to standard algorithms (44) (Table 4).

Acute circulatory failure associated with infection, referred to as septic shock, is characterized by an inad - equate tissue perfusion and oxygenation relative to met- abolic requirements. This imbalance between delivery and tissue uptake is mainly due to altered microvascular blood flow regulation as a result of dysregulated and/ or injured endothelial cells. Endothelial dysfunction is presumably induced by pathogenic bacterial products, inflammatory mediators, and reactive oxygen species produced by activated leukocytes [1]

In other words, in the presence of normal macro-hemodynamic, there may be regions of inadequate perfusion, underscoring the assessment of regional perfusion and oxygen deliv - ery at the organ level [3].

The rationale for peripheral perfusion monitoring is based on the fact that peripheral tissues, such as skin and muscles, are the first to suffer from impaired perfusion in severe infections. This is due to the absence of cutaneous circulation autoregulation and the early local vasocon - striction mediated by sympathetic neuroactivation [4].

several other mechanisms have shown to impair microvascular blood flow such as leukocyte adhesion, platelet activation and fibrin deposition. As the cutane - ous vascular bed plays an important role in the periph- eral thermoregulation, skin perfusion disorders during severe infections directly impact on skin color and/or temperature

Using laser Dop- pler imaging and NIRS (near-infrared spectroscopy) technology, both reduced perfusion and low tissue oxy - gen saturation in mottling areas, where demonstrated [5, 6]

The predictive value of the mottling score has also been reproduced in emergency departments, in non-selected critically ill patients [7] and more recently outside Europe [8]

Even in clinical conditions charac - terized by systemic vasodilation, mottling represents an increased risk of mortality.

In patients with cirrhosis, the mottling score remains a predictor of mortality dur- ing septic shock despite a lower sensitivity than non-cir- rhotic patients. The lower sensitivity could be explained by delayed mottling given the higher baseline skin perfu - sion in these patients [9].

In non- selected paediatric and critically ill adult patients, CRT was related to tissue perfusion, which was correlated to the plasma lactate level [10]

In septic shock patients, after initial resuscitation, CRT is a strong predictor of 14-day mortality with an area under the curve of 84 % (75–94) for the index tip measurement and 90 % (83–98) for the knee area measurement. In this study, a threshold of 2.4 s (index tip CRT) predicted mor - tality with a sensitivity of 82 % and a specificity of 73 %. When applied at the knee area, a CRT of 4.9 s predicted mortality with a sensitivity of 82 % and a specificity of 84 %. Most importantly, this study reported a good corre - lation between CRT and other parameters of tissue per- fusion like urinary output and lactate levels [13]

Finally, in a recent study in septic shock survivors, Hernandez et al. showed that survival was characterised by normali - sation of the CRT [14]

Although a few studies have related the subjective assessment of skin temperature to outcome, one of the problems of this approach, on top of the subjectiveness of this assessment, is that the temperature of the skin is affected by the outside (room temperature). Therefore, a difference between two temperatures is frequently used

Frequently, the difference between forearm and fingertip (Tskin-diff) is used to assess peripheral perfusion. Despite some dis - crepancies, several studies have shown that a Tskin-diff 0 °C is indicative of vasoconstriction whereas a Tskin- diff of more than 4 °C is associated with severe vasocon - striction. The advantage of this technique is that both spots of skin are similarly affected by room temperature

For example, in a preliminary study, Lima et al. reported that nitro - glycerin infusion normalised peripheral perfusion (maximal dose 16 mg/h). Twelve of the 15 patients (80 %) required a low dose (8 mg/h or less) to correct abnormal peripheral perfusion. Tskin-diff has also been used prospectively to guide fluid resuscitation in septic shock patients [16]

In this safety study including only 30 patients, it seemed that limiting the use of fluids in patients with normal peripheral perfusion was not only safe but was also associated with improved outcome parameters. The intervention group received less fluid in the treatment period as well as in the follow-up totalling almost 5 l less net positive fluid balance over the total study period of 72 h