**6. Further clinical and biochemical monitoring**

Meticulous monitoring of the patient's clinical and biochemical response to treatment is mandatory for timely adjustments in treatment as indicated by the patient's clinical or labo‐ ratory data. Documentation on a flow chart of hour-by-hour clinical observations, IV and or‐ al medications, fluids, and laboratory results is very helpful.

Monitoring should include the following [4]:

	- **◦** Headache

**•** Weigh the patient.

298 Type 1 Diabetes

**◦** hyperpnea

5% dehydration and acidosis are:

hypotension, and oliguria.

and hematocrit or complete blood count.

extracellular fluid (ECF) contraction.

**•** Mild DKA: venous pH <7.3 or bicarbonate <15 mmol/L

and may be used to monitor the response to treatment [25].

(ECG) for baseline evaluation of potassium status.

**•** Moderate DKA: pH <7.2, bicarbonate <10 mmol/L

**•** Severe DKA: pH <7.1, bicarbonate <5 mmol/L

**•** Perform a urinalysis for ketones.

fection.

*Supportive measures [1]:*

*Biochemical assessment [1,4]*

**◦** abnormal skin turgor ('tenting' or inelastic skin)

**•** Assess clinical severity of dehydration. Signs of dehydration include dry mucus mem‐ branes, sunken eyes, absent tears, weak pulses, and cool extremities. The three most use‐ ful individual signs for assessing dehydration in young children and predicting at least

**•** .≥10% dehydration is suggested by the presence of weak or impalpable peripheral pulses,

**•** Obtain a blood sample for laboratory measurement of serum or plasma glucose, electro‐ lytes, bicarbonate, blood urea nitrogen, creatinine, osmolality, venous (or arterial in criti‐ cally ill patient) pH, partial pressure of Carbon dioxide( pCO2), calcium, phosphorus, and magnesium concentrations (if possible), Glycosylated Hemoglobin (HbA1c), hemoglobin

**◦** Increased serum urea nitrogen and hematocrit may be useful markers of the severity of

**◦** It has to be noted that an elevated white blood cell count in response to stress is charac‐

**◦** Metabolic acidosis being an important landmark of DKA is also helpful to grade the se‐ verity of the condition and hence the prognosis by assessing its degree as follows [15]:

**•** Measurement of blood ß-OHB concentration, if available, is useful to confirm ketoacidosis

**•** Obtain appropriate specimens for culture (blood, urine, throat), if there is evidence of in‐

**•** If laboratory measurement of serum potassium is delayed, perform an electrocardiogram

**•** Secure the airway and empty the stomach by continuous nasogastric suction to prevent

pulmonary aspiration, in case there is deterioration in conscious level.

teristic of DKA and is not necessarily indicative of infection [24].

**◦** prolonged capillary refill time (normal capillary refill is < 1.5-2 seconds)

### **6.1. Laboratory tests**

**•** Serum electrolytes, glucose, blood urea nitrogen, hematocrit and blood gases should be repeated 2-hourly for the first 12 hours, or more frequently, as clinically indicated, in more severe cases.

**•** Shock with hemodynamic compromise is rare in pediatric DKA. If the patient is shocked, administer shock therapy: 10 ml/Kg 0.9% normal saline (or Ringer's lactate or acetate) through a large bore cannula, over 0.5 hr. Re-assess the patient and repeat up to a maxi‐

Diabetic Ketoacidosis: Clinical Practice Guidelines

http://dx.doi.org/10.5772/53020

301

**•** The volume and rate of administration depends on circulatory status and, where it is clin‐

Patients with DKA have a deficit in extracellular fluid (ECF) volume that usually is in the range 5–10%. Clinical estimates of the volume deficit are subjective and inaccurate,

Degree Fluids Degree Fluids

therefore, in moderate DKA use 5–7%and in severe DKA 7–10% dehydration [4].

**Dehydration Infants & children <8 years Children "/>8 years**

Mild 5% 50 ml/kg 3% 30 ml/kg Moderate 8% 80 ml/kg 5% 50 ml/kg Severe 10% 100 ml/kg 8% 80 ml/kg

> **Age (years) Amount of fluids** 0-2 80 ml/kg/24hr 3-5 70 ml/kg/24hr 6—9 60 ml/kg/24hr 10-14 50 ml/kg/24hr Adult ("/>15) 35 ml/kg/24hr

**3.** Total working fluid = deficit + maintenance (calculated for 48 hours)

mum of 30 ml/kg if necessary, with reassessment after each bolus.

weight) considering the age of the patient as shown in Table 1.

**Table 1.** Calculation of deficit fluid requirements in children presenting with DKA (1)

ically indicated.

**Degree of**

**•** Type of fluids

**• Calculate the Fluid Requirements**

**2.** Maintenance Fluid Requirements:

**Table 2.** Calculation of maintenance fluid requirements (1)

**1.** Deficit Fluid Requirements :

	- **◦ Anion gap = serum sodium(Na) {serum chloride (Cl) + serum bicarbonate (HCO3)} : normal is 12 ± 2 (mmol/L).** In DKA, the anion gap is typically 20–30 mmol/L; an anion gap >35 mmol/L suggests concomitant lactic acidosis.
	- **◦ Corrected sodium = measured Na + 2([plasma glucose -5.6]/5.6) (mmol/L)** The meas‐ ured serum sodium concentration is an unreliable index of the degree of ECF contrac‐ tion as glucose, largely restricted to the extracellular space, causes osmotic movement of water into the extracellular space thereby causing dilutional hyponatremia.
	- **◦** Therefore, it is important to calculate the corrected sodium (using the above formula) and monitor its changes throughout the course of therapy. As the plasma glucose con‐ centration decreases after administering fluid and insulin, the measured serum sodium concentration should increase (positive sodium load), but it is important to appreciate that this does not indicate a worsening of the hypertonic state. A failure of measured serum sodium levels to rise or a further decline in serum sodium levels with therapy is thought to be a potentially ominous sign of impending cerebral edema
	- **◦ Effective osmolality (mOsm/kg)= 2x(Na + K) + glucose (mmol/L)** The effective osmo‐ lality (formula above) is frequently in the range of 300–350 mOsm/Kg.

#### **6.2. Fluids and electrolytes**

*The objectives of fluid and electrolyte replacement therapy are [1]:*

#### **6.3. Fluids**

**•** Establish two I.V. lines: one for fluids and electrolytes and the other for insulin infusion


**5. Conclusion**

*Animal Models in Medicine and Biology*

the necessity to bear weight.

rial have not been discovered yet.

their application in load-bearing regions.

*4.2.3 Bioresorbable metals*

*4.2.1 Polymers*

*4.2.2 Ceramics*

after implantation. However, Ti and stainless steel implants have a higher e-modulus (Ti: e-modulus 100–124 GPa; steel: e-modulus 200 GPa) than bone (e-modulus 6–24 GPa). Moreover, permanent implants can cause "stress-shielding" leading to loss of bone under the plate or between bone and implant, thereby increasing the risk of refractures, designated as peri-prosthetic or peri-implant fractures [29, 31]. Moreover, the FDA has already described possible metallic sensitivity or allergic reactions linked to Ti-based alloys, such as Ti-6Al-4V [66], and studies using vanadium have also shown adverse effects [67]. However, resorbable materials exhibit functional properties by supporting bone formation and in-growth on a molecular level. To date there are only few resorbable materials used in cardiac, dental and neuro-surgery and some not weight-bearing application in orthopedic surgery, but adequate materials for orthopedic and trauma surgeries need good mechanical properties. Therefore, the main focus in biomaterial research is to evolve materials and tools to develop the optimal implant for the respective bone condition under

Poly-L-lactic acid (PLLA) and poly-lactic-co-glycolic acid (PLGA) are the most commonly used polymers considered for their use as osteosynthesis and bone grafts [68]. Disadvantages of polymers include poor mechanical properties (low strength and stiffness, high brittleness) and osteoconductivity. Degradation behavior depends on monomers and can be very slow thereby increasing the risk of adverse

Alternatively, polyhydroxybutyrate (PHB) can serve as a polymeric implant material, which is produced by microorganisms, especially bacteria. However, PHB can induce toxicological effects. However, these effects have been reduced dramatically, raising the potential for its application in clinics. Nevertheless, functional properties (i.e., osteoinductivity or osteoconductivity) of polymeric implant mate-

Ceramics are synthetic bone replacement materials with good biocompatibility and osteoconductivity, thereby showing good osseointegrative and nonimmunogenic effects. Composed of hydroxyapatite (HA), or alpha (α)- and beta (β)-tricalcium phosphates (TCP), ceramics exhibit poor mechanical properties including low yield strength and high brittleness, which make them unattractive for

In comparison to polymers and ceramics, iron (Fe), magnesium (Mg), and zinc (Zn) are more stable, tensile, and load-bearing, respectively. To process Fe-based alloys, the low melting point of Fe constitutes an interesting property. However, Hofstetter et al. demonstrated that limited access to oxygen was associated with slow degradation rates [70]. Metal implants based on Zn display several disadvantages including low rigidity and deformability, as well as corrosion inhibition. Therefore, Zn is likely more suited as an alloying element in combination with other materials. Finally, Mg-based alloys exhibit several advantages including good biocompatibility, resorbability, and favorable biomechanical properties. Moreover, some studies have demonstrated Mg's associated functional properties, especially its ability to support bone fracture healing [33]. For example, recent studies using

effects such as sclerotic areas in bone and fibrous encapsulation [69].

**34**

Here, we summarized fundamental differences in small and large animal models concerning bone quality, composition as well as their individual advantages and disadvantages. Focusing on two major complications in orthopedics and traumatology, we wanted to underline the merits of an animal model by supporting with scientific results obtained from our intensive literature recherché. Implant research is a hot topic in orthopedics and trauma surgery. Based on our expertise, we wanted to give insights into implant technology, materials, and designs. Currently, permanent implants are the state-of-the-art material used to stabilize bone fractures in orthopedics and trauma surgery. However, to develop the ideal implant for a certain bone condition (e.g., osteoporosis and osteoarthritis), the underlying disease and the detrimental outcome on bone (e.g., bone mass, fracture risk, and bone density) have to be taken into account when choosing the implant material (e.g., Ti-, Mg-, Fe-based implants), design (e.g., pin, screw, plate, and scaffold), material properties (e.g., tensile strength, non- or bio-resorbable), and implantation site (e.g., knee, femur, and tibia).

Hence, it is of utmost importance to choose the most appropriate animal model according to the research question and warranted primary outcome measures.


**2. Grid-Connected MG System**

Figure 1 shows the structure of the proposed grid-connected MG that includes DG, photovoltaic (PV), wind turbine (WT) units and controllable demands; it is connected to the main grid. MGOs can sell surplus power or buy insufficient power through interactions with the main grid, and they can request demand reduction from the customers using the DR program [28,29].

**Figure 1.** Proposed grid-connected microgrid (MG) system.


**3. Nonsurgical management**

There is a paucity of literature for the nonsurgical management of recurrent SUI following prior surgical repair. Most treatments are based on primary SUI studies, namely pelvic floor muscle training, weight loss, incontinence pessary and medications. These options have been systematically reviewed elsewhere. (Shamliyan et al. 2008)