| Objective and backgroundThe key factors of visceral secondary injury and death after severe burns are ischemiaand hypoxia，and shock is the most important reason for ischemia and hypoxia during theearly stage.It is well known that the occurrence of shock are closely related to the bloodvolume, cardiac pump function and vascular tone (reactivity), but the understanding of burnshock is not the case. Previously thought that, blood volume decrease of the burn shock wasprimarily due to the increased capillary permeability, plasma-like fluid in the intravascularleakage, resulting in a decrease in effective circulating blood volume. As there are noeffective measures to reduce capillary permeability so far, now fluid replacement therapy(Volume replacement) is the main treatment. In the circumstances of a serious shock or thelate stage of shock, the low vascular reactivity makes the expansion of the vascular bed,resulting in effective circulating blood volume to further reduce, and vasoactive drug can beused in this case. Another important factor for the shock is the heart pump function. Thetraditional view is that the heart does not appear to structural damage and organic dysfunction,does not participate in the occurrence of early shock. But a large number of clinical findingssuggest that, in many severe burn patients, even if given prompt fluid infusion after injury,shock is difficult to correct. Meanwhile the early myocardial damage indicators significantlyincreased and heart function reduced, suggesting that before the effective circulating bloodvolume decreased significantly, myocardial ischemia and hypoxia damage and dysfunctionhave occurred following severe burns. Because the heart is the power organ of the circulation,the early and prompt myocardial damage and heart dysfunction(before a significant reductionin effective circulating blood volume due to increased capillary permeability), not only causedcardiac dysfunction, but also induced or exacerbated the shock. It becomes one of theimportant factors to start early ischemia and hypoxia. Therefore, a "shock heart" hypothesis for ischemic and hypoxic damage of visceral organs and tissues during early stage followingsevere burns has been proposed. Thus, effective control of early postburn myocardial damageand dysfunction is an important part of prevention and treatment of burn shock. Based on theabove findings, the new protocol for burn shock resuscitation including "volume replacementplus cardiodynamic support" has been presented.Recent studies have shown that early application of small doses of enalaprilat injectionafter severe burns can improve the regional myocardial blood flow, reduce myocardialdamage and does not affect systemic blood pressure significantly. FDP injection can regulatecalcium dismetabolism of the myocardial cells, and inhibit cardiomyocyte apoptosis to reducemyocardial damage. Alprostadil injection can enhance the SOD activity of myocardial toreduce the MDA formation, improve the coronary circulation, and reduce myocardial damage.Therefore, we use these drugs for "cardiodynamic support".This subject is a clinical prospective randomized controlled trial (RCT), for immediateresuscitation and delayed resuscitation, analyze the efficacy and safety of the resuscitationprotocol, and then propose a new program of "volume replacement plus cardiodynamicsupport" for the burn shock resuscitation, and lay the foundation for the burn clinical therapyand improve the cure rate of severe burns.Materials and methodsHospitalized patients during December,2009to March,2012in burn unit of SouthwestHospital, Third Military Medical University were enrolled. Burn depth and surface area weredetermined according to clinic diagnostic criteria for burn patients. The selected hospitalizedpatients met the inclusion criteria as follows:①patients with age above18and under65years old, male or female;②patients with flame or hot liquid injury;③TBSA>30%withdeep second degree and third degree burn area≥20%);④At admission within6hourspostburn, or regular fluid resuscitation received prior to admission (immediate resuscitationgroup). At admission after6hours postburn, or irregular fluid resuscitation received whenadmitted (delayed resuscitation group);⑤Serum cTnI>0.15ug/L (positive) orCK-MB>25IU/L when admitted. The exclusion criteria are as follows:①patients withhistory of cardiovascular disease;②Patients suffering from hypertension, hypotension, orblood pressure fluctuations previously;③patients with age <18or>65;④Serum cTnI <0.15ug/L (negative) or CK-MB<25IU/L when admitted;⑤serious organic disease such as liver, kidney, lungs and other vital organs of the body;⑥patients with significant mentaldisorders, epilepsy and other symptoms;⑦lactating or pregnant female patients;⑧patientswho are allergic to experimental drugs or patients with corresponding contraindications;⑨patients dropped during the period of research;⑩other cases that are considered to be notsuitable for research. Termination criteria:①patients died;②patients do not fit (contrary tothe agreement or lost to follow) or for security reasons.Patients who met the inclusion criteria were divided into four groups randomly:immediate volume replacement (V group), immediate volume replacement pluscardiodynamic support (V+D group， including three subgroups enalapril, fructosediphosphate sodium, and alprostadil), delayed volume replacement (DV group), delayedvolume replacement plus cardiodynamic support (DV+D group). Cardiodynamic supportwere performed by application of1.25mg of enalaprilat(E) once a day，10g of FDP(F) twicea day or10ug of alprostadil(A) twice a day, lasting for3days. Indicators were observed andrecorded at admission, day1,2,3,7,14and21postburn respectively, including vital signs (T,P, R, BP recorded at6:00-8:00in the morning), LA, cTnI, CK, CK-MB, aHBDH, LDH, ALT,AST, GGT, Cr, BUN, β2-MG, AG, HCT, WBC, NEUT%, RBC, LYMPH%, and PLT.Statistical analysisAll data are expressed as (x±s) and analyzed using statistical software SPSS13.0.Probability values less than0.05were considered to be significant, and P <0.01were verysignificant.Results1. Immediate resuscitation1) Cases description: There were15effective cases in V group, the mean burn area was(45.07±4.58)%TBSA,20%of cases suffered more than51%TBSA burns, the mean Ⅲ°burn area was (11.00±4.34)%TBSA,4cases combined with inhalation injury, and2casesdied in3weeks after burn injury. There were55effective cases in V+D group (includingsubgroup enalapril14cases, fructose diphosphate sodium20cases, and alprostadi21cases),the mean burn area was (47.78±2.51)%TBSA,30.9%of cases suffered more than51%TBSAburns, the mean Ⅲ°burn area was (14.67±2.42)%TBSA,23cases combined with inhalationinjury, and no case died in3weeks after burn injury. Considering of the absolute value, theseverity of burn patients in V+D group was more severe than that in V group. However, there was no significant difference (p>0.05) in age, gender, injury factors, and inhalation injuryincidence, suggesting a good balance between immediate V group and immediate V+D group.2) Mortality: There was a13.30%(2/15) mortality in V group, however, in enalapril,fructose diphosphate sodium, and alprostadil treated groups, no patients died, suggesting thatthe resuscitation scheme of “volume replacement plus cardiodynamic support” significantlydecreased the mortality of burn patients in V+D group, even in the case of burn injury issevere than that in V group.3) Results of anti-shock indicators: Based on maintaining a satisfactory urine output,although there was a larger area and more severe burn injury, less fluid infusion volume in thethree treated subgroups and V+D group than those in V group was used, the urine output wasslightly more than that in V group, and there was no significant difference in blood pressureamong the three treated subgroups and the control, as well as V and V+D groups. Comparedwith V group, the serum level of lactate (LA) was significantly decreased in the three treatedsubgroups and V+D group (P <0.05) after admission; There were no significant difference (P>0.05) in RBC、HCT、HGB、WBC、body temperature, pulse, respiration rate and blood pressureamong the three treated subgroups and the control, as well as V and V+D groups.4) Laboratory results of organ functions: There were no differences among three kinds ofdrugs (enalapril,fructose diphosphate sodium, alprostadil)in laboratory results of organsfunctions. Compared with V group, the serum levels of cTnI, CK-MB, CK, a-HBDH andLDH were significantly decreased in in the three treated subgroups and V+D group (P <0.05);The serum level of β2-MG was significantly decreased in in the three treated subgroups andV+D group (P <0.05).2. Delayed resuscitation1) Cases description: There were also14effective cases in DV group (including threesubgroups enalapril, fructose diphosphate sodium, and alprostadil), the mean burn area was(48.00±3.90)%TBSA,35.70%of cases suffered more than51%TBSA burn, the mean Ⅲ°burn area was (16.00±4.98)%TBSA,3cases combined with inhalation injury, and2cases diedin3weeks after burn injury. There were effective48cases in DV+D group (includingsubgroup enalapril16cases, fructose diphosphate sodium17cases, and alprostadi15cases),the mean burn area was (59.13±3.08)%TBSA,62.50%of cases suffered more than51%TBSA burns, the mean Ⅲ°burn area was (23.06±3.19)%TBSA,25cases combined with inhalation injury, and2cases died in3weeks after burn injury. It is obvious that the severityof burn injury in DV+D group was more severe than that in DV group. However, there was nosignificant difference (p>0.05) in age, gender, injury factors, suggesting a good balancebetween DV group and DV+D group. However, there was a higher inhalation injury incidencein DV+D group than that in DV group (chi-square test, p>0.05).2) Mortality: The mortality in the control group was14.30%(2/14),5.90%(1/17) infructose diphosphate sodium treated subgroup,6.30%(1/16) in subgroup enalapril, and4.20%(2/48) in DV+D group, a10.10%decrease of mortality in DV+D group compared withthat in DV group, suggesting that the resuscitation scheme of “volume replacement pluscardiodynamic support” significantly decreased the mortality of burn patients suffering fromdelayed resuscitation, even in the case of burn injury is more severe than DV group.3) Results of anti-shock: after analyzing the fluid volume and urine output in the first andsecond24-hour of burn injury, based on maintaining a satisfactory urine output, althoughthere was a bigger area of burn injury in the three treated subgroups and DV+D group thanthose in DV group, the fluid infusion volume was slightly less in all the treated groups, but nosignificant differences were found among the treated groups. There was also no significantdifference in blood pressure in the three treated subgroups and DV+D group than those in DVgroup. Compared with DV group, the serum level of LA was significantly decreased in thethree treated subgroups and DV+D group (P <0.05), no significant differences were foundamong the three treated subgroups and the control, as well as V+D and V group. There wereno significant difference (P>0.05) in RBC、HCT、HGB、WBC、body temperature, pulse,respiration rate and blood pressure between groups in the observation period.4) Laboratory results of organs functions: There were no differences of parametersreflecting organs dysfunctions among the treated groups. Compared with DV group, theserum levels of cTnI, CK-MB, CK, a-HBDH and LDH were significantly decreased in thethree treated subgroups and DV+D group (P <0.05). The serum level of β2-MG was alsosignificantly decreased in the three treated subgroups and DV+D group (P <0.05).Discussion and conclusion1. Cardiodynamic supports plus fluid resuscitation attenuated ischemic and hypoxicdamage, promoted oxygenation or oxygen metabolism, reduced organ complications andimproved survival rate in severe burn patients. There were no differences among three kinds of drugs (enalapril, fructose diphosphate sodium, and alprostadil)in clinical efficacy.2. The recommended new resuscitation strategy to severe burn patients according to ourcurrent research is as following:1) for immediate resuscitation patients, the fluid volume of the first24h postburn (ml)=TBSA×boby weight(kg)×1.5+2000+cardiodynamic support drugs (enalapril or fructosediphosphate sodium or alprostadil)；the fluid volume of the second24h postburn (ml)=TBSA×boby weight(kg)×1.0+2000+cardiodynamic support drugs;2) for delayed resuscitation patients, the fluid volume of the first24h postburn (ml)=TBSA×boby weight (kg)×2.6+2000+cardiodynamic support drugs (enalapril or fructosediphosphate sodium or alprostadil)；the fluid volume of the second24h postburn (ml)=TBSA×boby weight(kg)×1.0+2000+cardiodynamic support drugs.3. Our prospective clinic research provided further evidence for the "shock heart"hypothesis for ischemic and hypoxic damage of visceral organs and tissues during early stagefollowing severe burns, and thus shed a new light for us to understand the underlyingmechanisms of burn shock. The recommended new strategy improved fluid resusciation andreduced organ complications, which may be therefore great significant for the treatment ofsevere burn patients. |
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